Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer

June 10, 2026 updated by: National Cancer Institute (NCI)

A Phase II/III Trial of Durvalumab and Chemotherapy for Patients With High Grade Upper Tract Urothelial Cancer Prior to Nephroureterectomy

This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) between patients with upper tract urothelial cancer (UTUC) randomized to neoadjuvant accelerated methotrexate, vinblastine, Adriamycin, cisplatin (aMVAC) alone or in combination with durvalumab. (Cisplatin eligible patients [Arms A and B]) II. Evaluation of pathologic complete response at radical nephroureterectomy (RNU) (pathologic complete response [pCR], ypT0N0/Nx). (Cisplatin ineligible patients [Arm C]).

SECONDARY OBJECTIVES:

I. To assess pathologic complete response (pCR) at surgery. (Cisplatin eligible cohort) II. Event-free survival (EFS) will be evaluated for the cisplatin ineligible cohort as a secondary endpoint. (Cisplatin ineligible cohort) III. Overall survival in all, and by post chemotherapy response (ypT0N0, yp =< T1N0, yp >= T2Nany). (All patients) IV. To evaluate disease-free survival (DFS) in each arm of the trial separately. (All patients) V. To evaluate cancer-specific survival of patients in each arm of the trial separately. (All patients) VI. To evaluate renal function outcomes following systemic treatment and following surgery ([RNU) in each arm of the trial separately. (All patients) VII. To evaluate safety and tolerability of neoadjuvant aMVAC alone or in combination with durvalumab prior to RNU. (All patients)

OUTLINE: Patients eligible for cisplatin are randomized to Arms A or B. Patients ineligible for cisplatin are assigned to Arm C.

ARM A: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

ARM B: Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

ARM C: Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

Patients also undergo tissue biopsy and blood sample collection on study, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed up within 30 days and then every 3-6 months for up to 5 years from study entry.

Study Type

Interventional

Enrollment (Estimated)

131

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Kingman, Arizona, United States, 86401
        • Recruiting
        • Kingman Regional Medical Center
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
    • Arkansas
      • Fort Smith, Arkansas, United States, 72903
        • Suspended
        • Mercy Hospital Fort Smith
      • Little Rock, Arkansas, United States, 72205
        • Active, not recruiting
        • University of Arkansas for Medical Sciences
    • California
      • Auburn, California, United States, 95602
        • Active, not recruiting
        • Sutter Auburn Faith Hospital
      • Berkeley, California, United States, 94704
        • Active, not recruiting
        • Alta Bates Summit Medical Center-Herrick Campus
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
        • Principal Investigator:
          • Abhishek Tripathi
        • Contact:
      • Fremont, California, United States, 94538
        • Active, not recruiting
        • Palo Alto Medical Foundation-Fremont
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Principal Investigator:
          • Aditya Bagrodia
        • Contact:
      • Modesto, California, United States, 95355
        • Active, not recruiting
        • Memorial Medical Center
      • Mountain View, California, United States, 94040
        • Active, not recruiting
        • Palo Alto Medical Foundation-Camino Division
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford Cancer Institute Palo Alto
        • Principal Investigator:
          • Ali R. Khaki
        • Contact:
      • Palo Alto, California, United States, 94301
        • Active, not recruiting
        • Palo Alto Medical Foundation Health Care
      • Roseville, California, United States, 95661
        • Active, not recruiting
        • Sutter Roseville Medical Center
      • Sacramento, California, United States, 95816
        • Active, not recruiting
        • Sutter Medical Center Sacramento
      • San Diego, California, United States, 92103
        • Recruiting
        • UC San Diego Medical Center - Hillcrest
        • Principal Investigator:
          • Aditya Bagrodia
        • Contact:
      • San Francisco, California, United States, 94115
        • Active, not recruiting
        • California Pacific Medical Center-Pacific Campus
      • Santa Cruz, California, United States, 95065
        • Active, not recruiting
        • Palo Alto Medical Foundation-Santa Cruz
      • Santa Rosa, California, United States, 95403
        • Active, not recruiting
        • Sutter Pacific Medical Foundation
      • Sunnyvale, California, United States, 94086
        • Active, not recruiting
        • Palo Alto Medical Foundation-Sunnyvale
      • Vallejo, California, United States, 94589
        • Active, not recruiting
        • Sutter Solano Medical Center/Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • UCHealth University of Colorado Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 720-848-0650
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Denver, Colorado, United States, 80206
        • Recruiting
        • UCHealth - Cherry Creek
        • Contact:
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Fort Collins, Colorado, United States, 80524
        • Recruiting
        • Poudre Valley Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 970-297-6150
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Fort Collins, Colorado, United States, 80528
        • Recruiting
        • Cancer Care and Hematology-Fort Collins
        • Contact:
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Greeley, Colorado, United States, 80631
        • Recruiting
        • UCHealth Greeley Hospital
        • Contact:
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Highlands Ranch, Colorado, United States, 80129
        • Recruiting
        • UCHealth Highlands Ranch Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 720-848-0650
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Lone Tree, Colorado, United States, 80124
        • Recruiting
        • UCHealth Lone Tree Health Center
        • Contact:
        • Principal Investigator:
          • Elizabeth R. Kessler
      • Loveland, Colorado, United States, 80538
        • Recruiting
        • Medical Center of the Rockies
        • Contact:
          • Site Public Contact
          • Phone Number: 970-203-7083
        • Principal Investigator:
          • Elizabeth R. Kessler
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • MedStar Washington Hospital Center
        • Contact:
          • Site Public Contact
          • Phone Number: 202-877-8839
        • Principal Investigator:
          • Suthee Rapisuwon
      • Washington D.C., District of Columbia, United States, 20016
        • Suspended
        • Sibley Memorial Hospital
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Active, not recruiting
        • Mayo Clinic in Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
        • Principal Investigator:
          • Jacqueline T. Brown
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory University Hospital Midtown
        • Contact:
          • Site Public Contact
          • Phone Number: 888-946-7447
        • Principal Investigator:
          • Jacqueline T. Brown
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory Saint Joseph's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 404-851-7115
        • Principal Investigator:
          • Jacqueline T. Brown
      • Decatur, Georgia, United States, 30033
    • Idaho
      • Nampa, Idaho, United States, 83687
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Nampa
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
    • Illinois
      • Alton, Illinois, United States, 62002
        • Suspended
        • OSF Saint Anthony's Health Center
      • Barrington, Illinois, United States, 60010
        • Recruiting
        • Advocate Good Shepherd Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 847-842-4847
        • Principal Investigator:
          • Thomas J. Saphner
      • Bloomington, Illinois, United States, 61704
        • Active, not recruiting
        • Illinois CancerCare-Bloomington
      • Burr Ridge, Illinois, United States, 60527
        • Active, not recruiting
        • Loyola Center for Health at Burr Ridge
      • Canton, Illinois, United States, 61520
        • Active, not recruiting
        • Illinois CancerCare-Canton
      • Carbondale, Illinois, United States, 62902
        • Suspended
        • Memorial Hospital of Carbondale
      • Carterville, Illinois, United States, 62918
        • Recruiting
        • SIH Cancer Institute
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Carthage, Illinois, United States, 62321
        • Active, not recruiting
        • Illinois CancerCare-Carthage
      • Centralia, Illinois, United States, 62801
        • Suspended
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60657
        • Recruiting
        • Advocate Illinois Masonic Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 773-296-5360
        • Principal Investigator:
          • Thomas J. Saphner
      • Crystal Lake, Illinois, United States, 60014
        • Recruiting
        • AMG Crystal Lake - Oncology
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Suspended
        • Decatur Memorial Hospital
      • Dixon, Illinois, United States, 61021
        • Active, not recruiting
        • Illinois CancerCare-Dixon
      • Downers Grove, Illinois, United States, 60515
        • Recruiting
        • Advocate Good Samaritan Hospital
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Elgin, Illinois, United States, 60123
        • Recruiting
        • Advocate Sherman Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 847-429-2907
        • Principal Investigator:
          • Thomas J. Saphner
      • Eureka, Illinois, United States, 61530
        • Active, not recruiting
        • Illinois CancerCare-Eureka
      • Galesburg, Illinois, United States, 61401
        • Suspended
        • Western Illinois Cancer Treatment Center
      • Galesburg, Illinois, United States, 61401
        • Active, not recruiting
        • Illinois CancerCare-Galesburg
      • Hazel Crest, Illinois, United States, 60429
        • Recruiting
        • Advocate South Suburban Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 708-799-9995
        • Principal Investigator:
          • Thomas J. Saphner
      • Homer Glen, Illinois, United States, 60491
        • Active, not recruiting
        • Loyola Medicine Homer Glen
      • Kewanee, Illinois, United States, 61443
        • Active, not recruiting
        • Illinois CancerCare-Kewanee Clinic
      • Libertyville, Illinois, United States, 60048
        • Recruiting
        • AMG Libertyville - Oncology
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Macomb, Illinois, United States, 61455
        • Active, not recruiting
        • Illinois CancerCare-Macomb
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Maywood, Illinois, United States, 60153
        • Active, not recruiting
        • Loyola University Medical Center
      • Melrose Park, Illinois, United States, 60160
        • Active, not recruiting
        • Marjorie Weinberg Cancer Center at Loyola-Gottlieb
      • Mount Vernon, Illinois, United States, 62864
        • Suspended
        • SSM Health Good Samaritan
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Oak Lawn, Illinois, United States, 60453-2699
        • Recruiting
        • Advocate Christ Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-323-8622
        • Principal Investigator:
          • Thomas J. Saphner
      • Ottawa, Illinois, United States, 61350
        • Active, not recruiting
        • Illinois CancerCare-Ottawa Clinic
      • Park Ridge, Illinois, United States, 60068
        • Recruiting
        • Advocate Lutheran General Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 847-384-3621
        • Principal Investigator:
          • Thomas J. Saphner
      • Pekin, Illinois, United States, 61554
        • Active, not recruiting
        • Illinois CancerCare-Pekin
      • Peoria, Illinois, United States, 61636
        • Suspended
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61615
        • Active, not recruiting
        • Illinois CancerCare-Peoria
      • Peru, Illinois, United States, 61354
        • Suspended
        • Valley Radiation Oncology
      • Peru, Illinois, United States, 61354
        • Active, not recruiting
        • Illinois CancerCare-Peru
      • Princeton, Illinois, United States, 61356
        • Active, not recruiting
        • Illinois CancerCare-Princeton
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 800-444-7541
      • Springfield, Illinois, United States, 62781
        • Suspended
        • Springfield Memorial Hospital
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Washington, Illinois, United States, 61571
        • Active, not recruiting
        • Illinois CancerCare - Washington
    • Indiana
      • Richmond, Indiana, United States, 47374
        • Active, not recruiting
        • Reid Health
    • Iowa
      • Ames, Iowa, United States, 50010
        • Active, not recruiting
        • Mary Greeley Medical Center
      • Ames, Iowa, United States, 50010
        • Active, not recruiting
        • McFarland Clinic - Ames
      • Bettendorf, Iowa, United States, 52722
        • Recruiting
        • University of Iowa Healthcare Cancer Services Quad Cities
        • Principal Investigator:
          • Fernando Maciel Barbosa
        • Contact:
      • Boone, Iowa, United States, 50036
        • Active, not recruiting
        • McFarland Clinic - Boone
      • Fort Dodge, Iowa, United States, 50501
        • Active, not recruiting
        • McFarland Clinic - Trinity Cancer Center
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Principal Investigator:
          • Fernando Maciel Barbosa
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
      • Jefferson, Iowa, United States, 50129
        • Active, not recruiting
        • McFarland Clinic - Jefferson
      • Marshalltown, Iowa, United States, 50158
        • Active, not recruiting
        • McFarland Clinic - Marshalltown
    • Kansas
      • Garden City, Kansas, United States, 67846
        • Suspended
        • Central Care Cancer Center - Garden City
      • Great Bend, Kansas, United States, 67530
        • Suspended
        • Central Care Cancer Center - Great Bend
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky/Markey Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 859-257-3379
        • Principal Investigator:
          • Patrick J. Hensley
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Recruiting
        • Mary Bird Perkins Cancer Center
        • Contact:
        • Principal Investigator:
          • Victor T. Lin
      • Metairie, Louisiana, United States, 70006
        • Recruiting
        • East Jefferson General Hospital
        • Contact:
        • Principal Investigator:
          • Rajasree P. Chowdry
      • Metairie, Louisiana, United States, 70006
        • Recruiting
        • LSU Healthcare Network / Metairie Multi-Specialty Clinic
        • Contact:
        • Principal Investigator:
          • Rajasree P. Chowdry
      • Metairie, Louisiana, United States, 70002
        • Recruiting
        • Mary Bird Perkins Cancer Center - Metairie
        • Principal Investigator:
          • Victor T. Lin
        • Contact:
          • Site Public Contact
          • Phone Number: 504-584-6990
      • New Orleans, Louisiana, United States, 70112
        • Recruiting
        • University Medical Center New Orleans
        • Contact:
        • Principal Investigator:
          • Rajasree P. Chowdry
    • Maine
      • Augusta, Maine, United States, 04330
        • Recruiting
        • Harold Alfond Center for Cancer Care
        • Contact:
          • Site Public Contact
          • Phone Number: 207-626-4855
        • Principal Investigator:
          • Erin Adler
      • Biddeford, Maine, United States, 04005
        • Suspended
        • MaineHealth Maine Medical Center - Biddeford
      • Sanford, Maine, United States, 04073
        • Recruiting
        • MaineHealth Cancer Care Center of York County
        • Contact:
          • Site Public Contact
          • Phone Number: 207-459-1600
        • Principal Investigator:
          • Erin Adler
      • Sanford, Maine, United States, 04073
        • Recruiting
        • MaineHealth Cancer Care and IV Therapy - Sanford
        • Contact:
        • Principal Investigator:
          • Erin Adler
      • Scarborough, Maine, United States, 04074
        • Recruiting
        • MaineHealth Maine Medical Center- Scarborough
        • Contact:
        • Principal Investigator:
          • Erin Adler
      • South Portland, Maine, United States, 04106
        • Recruiting
        • MaineHealth Cancer Care and IV Therapy - South Portland
        • Contact:
        • Principal Investigator:
          • Erin Adler
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Jean H. Hoffman-Censits
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • UMass Memorial Medical Center - University Campus
        • Contact:
        • Principal Investigator:
          • Kriti Mittal
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Recruiting
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Brighton, Michigan, United States, 48114
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Canton, Michigan, United States, 48188
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Chelsea, Michigan, United States, 48118
      • Clarkston, Michigan, United States, 48346
      • Clarkston, Michigan, United States, 48346
        • Suspended
        • Newland Medical Associates-Clarkston
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Hurley Medical Center
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Suspended
        • Genesee Hematology Oncology PC
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Cancer Hematology Centers - Flint
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Livonia, Michigan, United States, 48154
        • Suspended
        • Hope Cancer Clinic
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Macomb, Michigan, United States, 48044
        • Recruiting
        • Henry Ford Saint John Hospital - Macomb Medical
        • Principal Investigator:
          • Elie G. Dib
        • Contact:
      • Pontiac, Michigan, United States, 48341
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • Trinity Health Saint Joseph Mercy Oakland Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • Michigan Healthcare Professionals Pontiac
        • Principal Investigator:
          • Elie G. Dib
        • Contact:
      • Saginaw, Michigan, United States, 48604
        • Suspended
        • Oncology Hematology Associates of Saginaw Valley PC
      • Saginaw, Michigan, United States, 48601
      • Tawas City, Michigan, United States, 48764
      • West Branch, Michigan, United States, 48661
        • Suspended
        • Saint Mary's Oncology/Hematology Associates of West Branch
      • Ypsilanti, Michigan, United States, 48106
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Suspended
        • Fairview Ridges Hospital
      • Burnsville, Minnesota, United States, 55337
        • Suspended
        • Minnesota Oncology - Burnsville
      • Cambridge, Minnesota, United States, 55008
        • Suspended
        • Cambridge Medical Center
      • Coon Rapids, Minnesota, United States, 55433
        • Recruiting
        • Mercy Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Edina, Minnesota, United States, 55435
        • Suspended
        • Fairview Southdale Hospital
      • Fridley, Minnesota, United States, 55432
        • Active, not recruiting
        • Unity Hospital
      • Maple Grove, Minnesota, United States, 55369
        • Suspended
        • Fairview Clinics and Surgery Center Maple Grove
      • Maplewood, Minnesota, United States, 55109
        • Recruiting
        • Minnesota Oncology Hematology PA-Maplewood
        • Contact:
        • Principal Investigator:
          • David M. King
      • Maplewood, Minnesota, United States, 55109
        • Suspended
        • Saint John's Hospital - Healtheast
      • Minneapolis, Minnesota, United States, 55407
        • Suspended
        • Abbott-Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55415
        • Suspended
        • Hennepin County Medical Center
      • Minneapolis, Minnesota, United States, 55454
        • Suspended
        • Health Partners Inc
      • Monticello, Minnesota, United States, 55362
        • Suspended
        • Monticello Cancer Center
      • New Ulm, Minnesota, United States, 56073
        • Suspended
        • New Ulm Medical Center
      • Princeton, Minnesota, United States, 55371
        • Suspended
        • Fairview Northland Medical Center
      • Robbinsdale, Minnesota, United States, 55422
        • Suspended
        • North Memorial Medical Health Center
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Lance C. Pagliaro
      • Saint Louis Park, Minnesota, United States, 55416
        • Recruiting
        • Park Nicollet Clinic - Saint Louis Park
        • Contact:
        • Principal Investigator:
          • David M. King
      • Saint Paul, Minnesota, United States, 55101
        • Recruiting
        • Regions Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Saint Paul, Minnesota, United States, 55102
        • Suspended
        • United Hospital
      • Shakopee, Minnesota, United States, 55379
        • Suspended
        • Saint Francis Regional Medical Center
      • Stillwater, Minnesota, United States, 55082
        • Recruiting
        • Lakeview Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Waconia, Minnesota, United States, 55387
        • Suspended
        • Ridgeview Medical Center
      • Willmar, Minnesota, United States, 56201
        • Suspended
        • Rice Memorial Hospital
      • Woodbury, Minnesota, United States, 55125
        • Suspended
        • Minnesota Oncology Hematology PA-Woodbury
      • Wyoming, Minnesota, United States, 55092
        • Suspended
        • Fairview Lakes Medical Center
    • Missouri
      • Ballwin, Missouri, United States, 63011
        • Suspended
        • Mercy Oncology and Hematology - Clayton-Clarkson
      • Bolivar, Missouri, United States, 65613
        • Suspended
        • Central Care Cancer Center - Bolivar
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
      • Cape Girardeau, Missouri, United States, 63703
        • Suspended
        • Mercy Cancer Center - Cape Girardeau
      • Farmington, Missouri, United States, 63640
        • Recruiting
        • Parkland Health Center - Farmington
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Jefferson City, Missouri, United States, 65109
        • Suspended
        • MU Health Care Goldschmidt Cancer Center
      • Joplin, Missouri, United States, 64804
        • Suspended
        • Freeman Health System
      • Joplin, Missouri, United States, 64804
        • Suspended
        • Mercy Hospital Joplin
      • Rolla, Missouri, United States, 65401
        • Suspended
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Rolla, Missouri, United States, 65401
        • Suspended
        • Phelps Health Delbert Day Cancer Institute
      • Saint Joseph, Missouri, United States, 64506
        • Suspended
        • Heartland Regional Medical Center
      • Sainte Genevieve, Missouri, United States, 63670
        • Recruiting
        • Sainte Genevieve County Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Springfield, Missouri, United States, 65804
        • Suspended
        • Mercy Hospital Springfield
      • Springfield, Missouri, United States, 65807
        • Suspended
        • CoxHealth South Hospital
      • St Louis, Missouri, United States, 63128
        • Recruiting
        • Mercy Hospital South
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
      • St Louis, Missouri, United States, 63141
        • Recruiting
        • Mercy Hospital Saint Louis
        • Principal Investigator:
          • Jay W. Carlson
        • Contact:
          • Site Public Contact
          • Phone Number: 314-251-7066
      • St Louis, Missouri, United States, 63109
        • Suspended
        • Mercy Infusion Center - Chippewa
      • St Louis, Missouri, United States, 63131
        • Recruiting
        • Missouri Baptist Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sullivan, Missouri, United States, 63080
        • Recruiting
        • Missouri Baptist Sullivan Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sunset Hills, Missouri, United States, 63127
        • Recruiting
        • BJC Outpatient Center at Sunset Hills
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Washington, Missouri, United States, 63090
        • Suspended
        • Mercy Hospital Washington
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Recruiting
        • OptumCare Cancer Care at Charleston
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
      • Las Vegas, Nevada, United States, 89183
        • Recruiting
        • OptumCare Cancer Care at Fort Apache
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Completed
        • Hackensack University Medical Center
      • Livingston, New Jersey, United States, 07039
        • Recruiting
        • Saint Barnabas Medical Center
        • Principal Investigator:
          • Saum B. Ghodoussipour
        • Contact:
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Principal Investigator:
          • Saum B. Ghodoussipour
        • Contact:
          • Site Public Contact
          • Phone Number: 732-235-7356
      • Toms River, New Jersey, United States, 08755
        • Recruiting
        • Community Medical Center
        • Principal Investigator:
          • Saum B. Ghodoussipour
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Recruiting
        • University of New Mexico Cancer Center
        • Contact:
        • Principal Investigator:
          • Amy C. Tarnower
    • New York
      • Buffalo, New York, United States, 14263
        • Active, not recruiting
        • Roswell Park Cancer Institute
    • North Carolina
      • Clinton, North Carolina, United States, 28328
        • Recruiting
        • Southeastern Medical Oncology Center-Clinton
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Goldsboro, North Carolina, United States, 27534
        • Recruiting
        • Southeastern Medical Oncology Center-Goldsboro
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Jacksonville, North Carolina, United States, 28546
        • Recruiting
        • Southeastern Medical Oncology Center-Jacksonville
        • Principal Investigator:
          • Samer S. Kasbari
        • Contact:
      • Winston-Salem, North Carolina, United States, 27157
        • Active, not recruiting
        • Wake Forest University Health Sciences
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Recruiting
        • Miami Valley Hospital South
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Centerville, Ohio, United States, 45459
        • Active, not recruiting
        • Dayton Physicians LLC-Miami Valley South
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Miami Valley Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Recruiting
        • Miami Valley Hospital North
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Premier Blood and Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 937-276-8320
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Active, not recruiting
        • Dayton Physician LLC - Englewood
      • Findlay, Ohio, United States, 45840
        • Active, not recruiting
        • Armes Family Cancer Center
      • Franklin, Ohio, United States, 45005-1066
        • Recruiting
        • Atrium Medical Center-Middletown Regional Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Franklin, Ohio, United States, 45005
        • Active, not recruiting
        • Dayton Physicians LLC-Atrium
      • Greenville, Ohio, United States, 45331
        • Recruiting
        • Miami Valley Cancer Care and Infusion
        • Principal Investigator:
          • Tarek M. Sabagh
        • Contact:
          • Site Public Contact
          • Phone Number: 937-569-7515
      • Kettering, Ohio, United States, 45409
        • Active, not recruiting
        • Greater Dayton Cancer Center
      • Kettering, Ohio, United States, 45429
        • Active, not recruiting
        • Kettering Medical Center
      • Springfield, Ohio, United States, 45504
        • Suspended
        • Springfield Regional Cancer Center
      • Sylvania, Ohio, United States, 43560
        • Recruiting
        • ProMedica Flower Hospital
        • Contact:
        • Principal Investigator:
          • Jeffrey H. Muler
      • Troy, Ohio, United States, 45373
        • Recruiting
        • Upper Valley Medical Center
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
    • Oklahoma
      • Lawton, Oklahoma, United States, 73505
        • Recruiting
        • Cancer Centers of Southwest Oklahoma Research
        • Contact:
          • Site Public Contact
          • Phone Number: 877-231-4440
        • Principal Investigator:
          • Adanma Anji Ayanambakkam Attanathi
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Adanma Anji Ayanambakkam Attanathi
      • Oklahoma City, Oklahoma, United States, 73120
        • Suspended
        • Mercy Hospital Oklahoma City
    • Pennsylvania
      • Erie, Pennsylvania, United States, 16505
        • Recruiting
        • UPMC Hillman Cancer Center Erie
        • Principal Investigator:
          • Leonard J. Appleman
        • Contact:
      • Greensburg, Pennsylvania, United States, 15601
        • Recruiting
        • UPMC Cancer Centers - Arnold Palmer Pavilion
        • Contact:
          • Site Public Contact
          • Phone Number: 724-838-1900
        • Principal Investigator:
          • Leonard J. Appleman
      • Hershey, Pennsylvania, United States, 17033-0850
        • Recruiting
        • Penn State Milton S Hershey Medical Center
        • Contact:
        • Principal Investigator:
          • Monika Joshi
      • Monroeville, Pennsylvania, United States, 15146
        • Recruiting
        • UPMC Hillman Cancer Center - Monroeville
        • Principal Investigator:
          • Leonard J. Appleman
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • William J. Tester
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania/Abramson Cancer Center
        • Principal Investigator:
          • Ronac Mamtani
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Cancer Institute (UPCI)
        • Contact:
          • Site Public Contact
          • Phone Number: 412-647-8073
        • Principal Investigator:
          • Leonard J. Appleman
      • Pittsburgh, Pennsylvania, United States, 15237
        • Recruiting
        • UPMC-Passavant Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 412-367-6454
        • Principal Investigator:
          • Leonard J. Appleman
      • Pittsburgh, Pennsylvania, United States, 15243
        • Recruiting
        • UPMC-Saint Clair Hospital Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 412-502-3920
        • Principal Investigator:
          • Leonard J. Appleman
      • Washington, Pennsylvania, United States, 15301
        • Recruiting
        • UPMC Cancer Center-Washington
        • Contact:
        • Principal Investigator:
          • Leonard J. Appleman
      • West Reading, Pennsylvania, United States, 19611
        • Recruiting
        • Reading Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 610-988-9323
        • Principal Investigator:
          • Terrence P. Cescon
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Active, not recruiting
        • Medical University of South Carolina
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Contact:
        • Principal Investigator:
          • Vitaly Margulis
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Parkland Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Vitaly Margulis
      • Dallas, Texas, United States, 75237
        • Suspended
        • UT Southwestern Simmons Cancer Center - RedBird
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Fort Worth
        • Contact:
        • Principal Investigator:
          • Vitaly Margulis
      • Richardson, Texas, United States, 75080
        • Recruiting
        • UT Southwestern Clinical Center at Richardson/Plano
        • Contact:
        • Principal Investigator:
          • Vitaly Margulis
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center - Montlake
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-8824
        • Principal Investigator:
          • Petros Grivas
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-8824
        • Principal Investigator:
          • Petros Grivas
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • Recruiting
        • West Virginia University Charleston Division
        • Contact:
          • Site Public Contact
          • Phone Number: 304-388-9944
        • Principal Investigator:
          • Kok Hoe Chan
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • Recruiting
        • ThedaCare Regional Cancer Center
        • Contact:
        • Principal Investigator:
          • Matthias Weiss
      • Burlington, Wisconsin, United States, 53105
        • Recruiting
        • Aurora Cancer Care-Southern Lakes VLCC
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Eau Claire, Wisconsin, United States, 54701
      • Germantown, Wisconsin, United States, 53022
        • Recruiting
        • Aurora Health Care Germantown Health Center
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Grafton, Wisconsin, United States, 53024
        • Recruiting
        • Aurora Cancer Care-Grafton
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Green Bay, Wisconsin, United States, 54311
        • Recruiting
        • Aurora BayCare Medical Center
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Kenosha, Wisconsin, United States, 53142
        • Recruiting
        • Aurora Cancer Care-Kenosha South
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Marinette, Wisconsin, United States, 54143
        • Recruiting
        • Aurora Bay Area Medical Group-Marinette
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Marshfield, Wisconsin, United States, 54449
      • Milwaukee, Wisconsin, United States, 53209
        • Recruiting
        • Aurora Cancer Care-Milwaukee
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Milwaukee, Wisconsin, United States, 53215
        • Recruiting
        • Aurora Saint Luke's Medical Center
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Milwaukee, Wisconsin, United States, 53233
        • Recruiting
        • Aurora Sinai Medical Center
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Minocqua, Wisconsin, United States, 54548
      • Mukwonago, Wisconsin, United States, 53149
        • Recruiting
        • ProHealth D N Greenwald Center
        • Contact:
        • Principal Investigator:
          • Timothy R. Wassenaar
      • New Richmond, Wisconsin, United States, 54017
        • Suspended
        • Cancer Center of Western Wisconsin
      • Oconomowoc, Wisconsin, United States, 53066
        • Recruiting
        • ProHealth Oconomowoc Memorial Hospital
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:
          • Site Public Contact
          • Phone Number: 262-928-7878
      • Oshkosh, Wisconsin, United States, 54904
        • Recruiting
        • Vince Lombardi Cancer Clinic - Oshkosh
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Racine, Wisconsin, United States, 53406
        • Recruiting
        • Aurora Cancer Care-Racine
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Rice Lake, Wisconsin, United States, 54868
      • Sheboygan, Wisconsin, United States, 53081
        • Recruiting
        • Vince Lombardi Cancer Clinic-Sheboygan
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Stevens Point, Wisconsin, United States, 54482
      • Summit, Wisconsin, United States, 53066
        • Recruiting
        • Aurora Medical Center in Summit
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Two Rivers, Wisconsin, United States, 54241
        • Recruiting
        • Vince Lombardi Cancer Clinic-Two Rivers
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Waukesha, Wisconsin, United States, 53188
        • Recruiting
        • ProHealth Waukesha Memorial Hospital
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:
          • Site Public Contact
          • Phone Number: 262-928-7632
      • Waukesha, Wisconsin, United States, 53188
        • Recruiting
        • UW Cancer Center at ProHealth Care
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:
      • Waupaca, Wisconsin, United States, 54981
        • Recruiting
        • ThedaCare Cancer Care - Waupaca
        • Contact:
        • Principal Investigator:
          • Matthias Weiss
      • Wauwatosa, Wisconsin, United States, 53226
        • Recruiting
        • Aurora Cancer Care-Milwaukee West
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • West Allis, Wisconsin, United States, 53227
        • Recruiting
        • Aurora West Allis Medical Center
        • Contact:
        • Principal Investigator:
          • Thomas J. Saphner
      • Weston, Wisconsin, United States, 54476

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • STEP 1 REGISTRATION AND RANDOMIZATION
  • Patients must be >= 18 years of age
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

  • Patient must have a diagnosis of high grade upper tract urothelial carcinoma expected within 14 weeks (98 days) prior to registration/randomization with one of the following:

    • Biopsy (gold standard, preferred) and either upper urinary tract mass on cross-sectional imaging or tumor directly visualized during upper urinary tract endoscopy

    • High grade cytology and clinically estimated invasive upper urinary tract mass on cross-sectional imaging (e.g., including presence of tumor-related hydronephrosis) or tumor directly visualized during upper urinary tract endoscopy

      • NOTE: Universal histologic testing of UTUC with additional studies, such as immunohistochemistry and/or microsatellite instability, is strongly recommended to identify patients with high probability of Lynch-related or other germline mutation related cancers whom clinicians should refer for genetic counseling and germline testing (this is not required for eligibility)

        • Due to the anatomy of upper urinary tract and lack of muscularis propria, pathologic evidence of cT2 on biopsy is usually not possible
  • Patients must not have any component of small cell/neuroendocrine carcinoma. Other histologic subtypes (variants) are permitted provided the half or predominant (>= 50%) subtype is conventional urothelial carcinoma
  • Leukocytes >= 3,000/mcL (obtained =< 14 days prior to registration/randomization)
  • Platelets >= 100,000/mcL (obtained =< 14 days prior to registration/randomization)
  • Total bilirubin =< 1.2 mg/dL (or ≤ 2 mg/dLfor patients with Gilbert's disease)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x institutional ULN (obtained =< 14 days prior to registration/randomization)

  • Hemoglobin (Hgb) >= 9 g/dL (obtained =< 14 days prior to registration/randomization)

    • NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
  • Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment

  • Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings >=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) scan or other imaging or other criteria can be eligible based on investigator discretion).

    • NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scan to evaluate for bone metastasis at the discretion of local provider.

  • Patient must meet below criteria for prior/current malignancy history:

    • Non-urothelial cancer malignancy history:

      • Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat

        • NOTE: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

      • Urothelial cancer malignancy history:

        • Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
        • T0, Ta or Tis at any time
        • T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy [e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)]. Prior systemic immune checkpoint inhibitor is not allowed.
        • Patient with history of >= pT4b, N+, and/or M1 UC is not eligible.
        • NOTE: Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (< cT1 N0) are eligible regardless of time elapsed
  • Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations in the three months prior to registration that would limit compliance with study requirements
  • Patient must not have received prior radiation therapy to >= 25% of the bone marrow for other diseases

  • Patient must not have received prior systemic anthracycline therapy

    • NOTE: Patients who have received prior intravesical therapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
  • Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease [IBD], e.g. ulcerative colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible

  • Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion and are allowed:

    • Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g. intra-articular injection
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
    • Steroids as pre-medications for hypersensitivity reactions (e.g. computed tomography [CT] pre-medication)

  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial

    • NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
    • NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within 7 days of registration/randomization

  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

    • NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab

  • Patient must not have had a major surgical procedure within 28 days prior to registration/randomization

    • NOTE: Cystoscopy/ureteroscopy/TURBT, stent placement or nephrostomy tube is not considered major surgery
  • Patient must not have history of allogenic organ transplantation
  • Patient must have a body weight of > 30 kg
  • Patient must have life expectancy of >= 12 weeks

  • Patient must have creatinine clearance > 15 ml/min as estimated by Cockcroft-Gault formula or glomerular filtration rate (GFR) > 15 ml/min/1.73m^2 within 28 days prior to registration/randomization

    • NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with recommended cisplatin contraindications. Patients who are cisplatin-eligible will be randomized to either Arm A or Arm B and patients who are cisplatin-ineligible will be registered to Arm C

      • Patients that meet any of the following four criteria will be registered to the cisplatin-ineligible Arm C if they meet other eligibility criteria:

        • Creatinine clearance > 15 ml/min and =< 50 ml/min (estimated by Cockcroft-Gault formula) or GFR > 15ml/min/1.73m^2 and ≤ 50 ml/min/1.73 m^2
        • Hearing loss >= 3
        • Neuropathy >= 2
        • ECOG performance status 2
      • In addition, the patient must have an absolute neutrophil count (ANC) >= 1,000/mcL obtained =< 14 days prior to registration

      • Patients that meet all of the following four criteria will be randomized to the cisplatin-eligible Arm A or Arm B:

        • Creatinine clearance > 50ml/min (estimated by Cockcroft-Gault formula) or GFR > 50ml/min/1.73m^2
        • ECOG performance status 0-1
        • Hearing loss grade 0-2
        • Neuropathy 0-1
      • In addition, the patient must have an absolute neutrophil count (ANC) >= 1,500/mcL obtained =< 14 days prior to randomization
      • Also, the patient must have left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (durvalumab, chemotherapy)
Patients receive durvalumab IV over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736
  • MEDI 4736
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Drug: Doxorubicin Hydrochloride
Given Iv
Other Names:
  • Adriamycin
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
  • FI106
Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Jylamvo
Biological: Pegfilgrastim
Given via injection
Other Names:
  • Filgrastim SD-01
  • filgrastim-SD/01
  • Fulphila
  • HSP-130
  • Jinyouli
  • Neulasta
  • Neulastim
  • Nyvepria
  • PEG-filgrastim
  • Pegcyte
  • Pegfilgrastim Biosimilar HSP-130
  • Pegfilgrastim Biosimilar Nyvepria
  • Pegfilgrastim Biosimilar Pegcyte
  • Pegfilgrastim Biosimilar PF-06881894
  • Pegfilgrastim Biosimilar Udenyca
  • Pegfilgrastim Biosimilar Ziextenzo
  • Pegfilgrastim-jmdb
  • PF-06881894
  • SD-01
  • SD-01 sustained duration G-CSF
  • Udenyca
  • Ziextenzo
  • Neupopeg
  • Pegylated G-CSF
  • Pegylated GCSF
  • Pegylated Granulocyte Colony Stimulating Factor
  • Pegfilgrastim-apgf
  • Pegfilgrastim-bmez
  • Pegfilgrastim-cbqv
  • Dulastin
  • Tripegfilgrastim
  • Fylnetra
  • G-Lasta
  • Pegfilgrastim-fpgk
  • Pegfilgrastim-pbbk
  • Stimufend
  • Pegfilgrastim-cegf
  • Pegfilgrastim-dyru
  • Pegfilgrastim-gras
  • Pegfilgrastim-pelg
  • Pegfilgrastim-pelm
Drug: Vinblastine Sulfate
Given Iv
Other Names:
  • 29060 LE
  • 29060-LE
  • Exal
  • Velban
  • Velbe
  • Velsar
  • VINCALEUKOBLASTINE
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy
Active Comparator: Arm B (chemotherapy)
Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Drug: Doxorubicin Hydrochloride
Given Iv
Other Names:
  • Adriamycin
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
  • FI106
Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Jylamvo
Biological: Pegfilgrastim
Given via injection
Other Names:
  • Filgrastim SD-01
  • filgrastim-SD/01
  • Fulphila
  • HSP-130
  • Jinyouli
  • Neulasta
  • Neulastim
  • Nyvepria
  • PEG-filgrastim
  • Pegcyte
  • Pegfilgrastim Biosimilar HSP-130
  • Pegfilgrastim Biosimilar Nyvepria
  • Pegfilgrastim Biosimilar Pegcyte
  • Pegfilgrastim Biosimilar PF-06881894
  • Pegfilgrastim Biosimilar Udenyca
  • Pegfilgrastim Biosimilar Ziextenzo
  • Pegfilgrastim-jmdb
  • PF-06881894
  • SD-01
  • SD-01 sustained duration G-CSF
  • Udenyca
  • Ziextenzo
  • Neupopeg
  • Pegylated G-CSF
  • Pegylated GCSF
  • Pegylated Granulocyte Colony Stimulating Factor
  • Pegfilgrastim-apgf
  • Pegfilgrastim-bmez
  • Pegfilgrastim-cbqv
  • Dulastin
  • Tripegfilgrastim
  • Fylnetra
  • G-Lasta
  • Pegfilgrastim-fpgk
  • Pegfilgrastim-pbbk
  • Stimufend
  • Pegfilgrastim-cegf
  • Pegfilgrastim-dyru
  • Pegfilgrastim-gras
  • Pegfilgrastim-pelg
  • Pegfilgrastim-pelm
Drug: Vinblastine Sulfate
Given Iv
Other Names:
  • 29060 LE
  • 29060-LE
  • Exal
  • Velban
  • Velbe
  • Velsar
  • VINCALEUKOBLASTINE
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy
Experimental: Arm C (durvalumab, gemcitabine hydrochloride)
Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • Gemzar
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemcitabine HCI
  • LY-188011
  • LY188011
  • LY 188011
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736
  • MEDI 4736
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Therapeutic Conventional Surgery
Undergo surgery
Procedure: Biopsy Procedure
Undergo tissue biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
  • Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic complete response (pCR) (Cisplatin ineligible cohort: Arm C)
Time Frame: At surgery
Will assess pathologic complete response at surgery (pCR, pT0N0/Nx) by local pathology review. Patients who drop out prior to surgery or who have unknown response status will be considered as non-responders.
At surgery
Event-free survival (EFS) (Cisplatin eligible cohort: Arms A and B)
Time Frame: From registration/randomization to the earliest of systemic recurrence outside urinary tract, cancer progression, or death from any cause, assessed up to 5 years
Disease progression prior to surgery or omission of surgery due to unresectable tumors, muscle-invasive cancer or disease recurring outside of the bladder, urethra, or contralateral upper tract are considered as events for EFS.
From registration/randomization to the earliest of systemic recurrence outside urinary tract, cancer progression, or death from any cause, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pCR (Cisplatin-eligible cohort: Arms A and B)
Time Frame: Up to 5 years
Up to 5 years
Urothelial cancer-free survival or disease-free survival (All Patients)
Time Frame: From the date of surgery to the earlier of a return of upper tract urothelial cancer (UTUC) or death from any cause, assessed up to 5 years
A return of UTUC includes non-muscle invasive recurrences, pathologic T2 or higher muscle-invasive recurrences specifically in the urinary tract, metastatic disease outside the urinary tract, or death. Patients alive without documented UTUC will be censored at the date of last disease assessment.
From the date of surgery to the earlier of a return of upper tract urothelial cancer (UTUC) or death from any cause, assessed up to 5 years
Renal function outcomes following systemic treatment and following radical nephroureterectomy (All Patients)
Time Frame: Post chemotherapy and post surgery
The proportion of patients with renal insufficiency (creatinine [CrCl] < 60 ml/min) post chemotherapy and post nephroureterectomy as well as the proportion of patients with renal function improvement (CrCl < 60 ml/min at baseline and CrCl >= 60 ml/min on study) will be reported along with exact binomial confidence intervals. The distribution of changes in renal function post chemotherapy as well as post surgery from baseline will also be reported. The analysis of renal function outcomes will be performed among patients who receive at least one dose of study therapy.
Post chemotherapy and post surgery
Incidence of adverse events (All Patients)
Time Frame: Up to 30 days post surgery
Toxicity will be evaluated in all treated patients.
Up to 30 days post surgery
EFS (cisplatin-ineligible cohort: Arm C)
Time Frame: From registration/randomization to the earliest of systemic recurrence outside urinary tract, cancer progression, or death from any cause, assessed up to 5 years
Will be characterized using the Kaplan-Meier method.
From registration/randomization to the earliest of systemic recurrence outside urinary tract, cancer progression, or death from any cause, assessed up to 5 years
Overall survival (OS) (All Patients)
Time Frame: From registration/randomization to death from any cause, assessed up to 5 years
OS will be evaluated by arm, post chemotherapy response (ypCR, stage yp =< T1N0, yp >= T2N0), as well as stage (ypCR and > ypCR) within and across treatment arms. Will be estimated using Kaplan-Meier method.
From registration/randomization to death from any cause, assessed up to 5 years
Cancer-specific survival (All Patients)
Time Frame: From registration/randomization to death due to cancer; deaths due to other causes will be counted as competing events, assessed up to 5 years
Will be analyzed using Gray's method and cumulative incidence estimates will be reported.
From registration/randomization to death due to cancer; deaths due to other causes will be counted as competing events, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jean H Hoffman-Censits, ECOG-ACRIN Cancer Research Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2021

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

November 13, 2020

First Submitted That Met QC Criteria

November 13, 2020

First Posted (Actual)

November 16, 2020

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 10, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2020-09850 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180820 (U.S. NIH Grant/Contract)
  • EA8192 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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