Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations

April 9, 2026 updated by: Alliance for Clinical Trials in Oncology

A Phase II Study of Gemcitabine Plus Cisplatin Chemotherapy in Patients With Muscle-invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations

This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the 3-year event free survival, defined as the proportion of patients without invasive or metastatic recurrence following definitive gemcitabine hydrochloride (gemcitabine) and cisplatin (standard or dose-dense) chemotherapy in those patients whose pre-treatment transurethral resection of bladder tumor (TURBT) tumors harbor deleterious DDR gene alterations and who achieve < cT1 response to chemotherapy.

SECONDARY OBJECTIVES:

I. To determine the clinical response rate (< cT1) for patients harboring deleterious DDR gene alterations following dose dense gemcitabine and cisplatin.

II. To determine the bladder-intact and overall survival for DDR-altered patients with < cT1.

III. For DDR gene altered patients who elect radical cystectomy despite < cT1, to determine the pT0 rate in this patient population.

IV. To determine the pathologic response rate at cystectomy and 3-year recurrence-free and overall survival for patients without DDR mutations who are registered onto this trial.

V. To assess the local treatment burden (Bacillus Calmette-Guerin [BCG] therapy, resection of non-invasive disease, checkpoint blockade) over time in the bladder-sparing group.

VI. To determine the bladder-intact disease-free survival in patients who elect to undergo chemoradiation therapy in the DDR mutant group and the DDR wild-type group.

OUTLINE:

Participants receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim subcutaneously (SC) on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants are then assigned to 1 of 2 arms.

ARM I: Participants with DDR gene alteration and disease stage < cT1 undergo bladder sparing.

ARM II: Participants with DDR gene alteration and disease stage >= cT1 or participants without DDR gene alteration undergo radical cystectomy or chemoradiotherapy.

After completion of study treatment, participants are followed up for 5 years.

Study Type

Interventional

Enrollment (Actual)

237

Phase

Phase 2

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
- Alaska
  - Fairbanks, Alaska, United States, 99701
    - Fairbanks Memorial Hospital
- Arizona
  - Goodyear, Arizona, United States, 85338
    - CTCA at Western Regional Medical Center
  - Phoenix, Arizona, United States, 85004
    - Cancer Center at Saint Joseph's
- Arkansas
  - Fort Smith, Arkansas, United States, 72903
    - Mercy Hospital Fort Smith
  - Hot Springs, Arkansas, United States, 71913
    - CHI Saint Vincent Cancer Center Hot Springs
  - Little Rock, Arkansas, United States, 72205
    - University of Arkansas for Medical Sciences
- California
  - Arroyo Grande, California, United States, 93420
    - Mission Hope Medical Oncology - Arroyo Grande
  - Carmichael, California, United States, 95608
    - Mercy San Juan Medical Center
  - Carmichael, California, United States, 95608
    - Mercy Cancer Center - Carmichael
  - Elk Grove, California, United States, 95758
    - Mercy Cancer Center - Elk Grove
  - Los Angeles, California, United States, 90048
    - Cedars Sinai Medical Center
  - Martinez, California, United States, 94553-3156
    - Contra Costa Regional Medical Center
  - Marysville, California, United States, 95901
    - Fremont - Rideout Cancer Center
  - Merced, California, United States, 95340
    - Mercy Cancer Center
  - Rocklin, California, United States, 95765
    - Mercy Cancer Center - Rocklin
  - Sacramento, California, United States, 95817
    - University of California Davis Comprehensive Cancer Center
  - Sacramento, California, United States, 95816
    - Mercy Cancer Center - Sacramento
  - San Luis Obispo, California, United States, 93401
    - Pacific Central Coast Health Center-San Luis Obispo
  - Santa Maria, California, United States, 93444
    - Mission Hope Medical Oncology - Santa Maria
  - Stockton, California, United States, 95204
    - Saint Joseph's Medical Center
  - Walnut Creek, California, United States, 94598
    - BASS Medical Group - Lennon
  - Woodland, California, United States, 95695
    - Woodland Memorial Hospital
- Colorado
  - Aurora, Colorado, United States, 80012
    - Rocky Mountain Cancer Centers-Aurora
  - Aurora, Colorado, United States, 80012
    - The Medical Center of Aurora
  - Boulder, Colorado, United States, 80304
    - Rocky Mountain Cancer Centers-Boulder
  - Colorado Springs, Colorado, United States, 80907
    - Penrose-Saint Francis Healthcare
  - Colorado Springs, Colorado, United States, 80907
    - Rocky Mountain Cancer Centers-Penrose
  - Colorado Springs, Colorado, United States, 80923
    - Saint Francis Cancer Center
  - Denver, Colorado, United States, 80218
    - Presbyterian - Saint Lukes Medical Center - Health One
  - Denver, Colorado, United States, 80210
    - AdventHealth Porter
  - Durango, Colorado, United States, 81301
    - Mercy Medical Center
  - Durango, Colorado, United States, 81301
    - CommonSpirit Cancer Center Mercy
  - Englewood, Colorado, United States, 80113
    - Mountain Blue Cancer Care Center - Swedish
  - Englewood, Colorado, United States, 80113
    - Swedish Medical Center
  - Englewood, Colorado, United States, 80113
    - The Melanoma and Skin Cancer Institute
  - Golden, Colorado, United States, 80401
    - Mountain Blue Cancer Care Center
  - Greeley, Colorado, United States, 80631
    - Banner North Colorado Medical Center
  - Lakewood, Colorado, United States, 80228
    - Saint Anthony Hospital
  - Lakewood, Colorado, United States, 80228
    - Rocky Mountain Cancer Centers-Lakewood
  - Littleton, Colorado, United States, 80120
    - Rocky Mountain Cancer Centers-Littleton
  - Littleton, Colorado, United States, 80122
    - AdventHealth Littleton
  - Lone Tree, Colorado, United States, 80124
    - Sky Ridge Medical Center
  - Longmont, Colorado, United States, 80501
    - Longmont United Hospital
  - Longmont, Colorado, United States, 80501
    - Rocky Mountain Cancer Centers-Longmont
  - Loveland, Colorado, United States, 80539
    - Banner North Colorado Medical Center - Loveland Campus
  - Parker, Colorado, United States, 80138
    - Rocky Mountain Cancer Centers-Parker
  - Parker, Colorado, United States, 80138
    - AdventHealth Parker
  - Pueblo, Colorado, United States, 81004
    - Saint Mary Corwin Medical Center
  - Pueblo, Colorado, United States, 81008
    - Rocky Mountain Cancer Centers - Pueblo
  - Thornton, Colorado, United States, 80260
    - Rocky Mountain Cancer Centers-Thornton
  - Westminster, Colorado, United States, 80023
    - Saint Anthony North Hospital
- Connecticut
  - Hartford, Connecticut, United States, 06102
    - Hartford Hospital
  - Meriden, Connecticut, United States, 06451
    - Midstate Medical Center
  - New Britain, Connecticut, United States, 06050
    - The Hospital of Central Connecticut
  - Norwich, Connecticut, United States, 06360
    - William Backus Hospital
- Florida
  - Fort Lauderdale, Florida, United States, 33308
    - Holy Cross Hospital
  - Gainesville, Florida, United States, 32610
    - UF Health Cancer Institute - Gainesville
- Idaho
  - Boise, Idaho, United States, 83706
    - Saint Alphonsus Cancer Care Center-Boise
  - Caldwell, Idaho, United States, 83605
    - Saint Alphonsus Cancer Care Center-Caldwell
  - Coeur d'Alene, Idaho, United States, 83814
    - Kootenai Health - Coeur d'Alene
  - Emmett, Idaho, United States, 83617
    - Walter Knox Memorial Hospital
  - Meridian, Idaho, United States, 83642
    - Idaho Urologic Institute-Meridian
  - Nampa, Idaho, United States, 83687
    - Saint Alphonsus Cancer Care Center-Nampa
  - Post Falls, Idaho, United States, 83854
    - Kootenai Clinic Cancer Services - Post Falls
  - Sandpoint, Idaho, United States, 83864
    - Kootenai Clinic Cancer Services - Sandpoint
- Illinois
  - Alton, Illinois, United States, 62002
    - OSF Saint Anthony's Health Center
  - Aurora, Illinois, United States, 60504
    - Rush-Copley Medical Center
  - Bloomington, Illinois, United States, 61704
    - Illinois CancerCare-Bloomington
  - Canton, Illinois, United States, 61520
    - Illinois CancerCare-Canton
  - Carbondale, Illinois, United States, 62902
    - Memorial Hospital of Carbondale
  - Carterville, Illinois, United States, 62918
    - SIH Cancer Institute
  - Carthage, Illinois, United States, 62321
    - Illinois CancerCare-Carthage
  - Centralia, Illinois, United States, 62801
    - Centralia Oncology Clinic
  - Centralia, Illinois, United States, 62801
    - Saint Mary's Hospital
  - Chicago, Illinois, United States, 60612
    - University of Illinois
  - Danville, Illinois, United States, 61832
    - Carle at The Riverfront
  - Decatur, Illinois, United States, 62526
    - Decatur Memorial Hospital
  - Decatur, Illinois, United States, 62526
    - Cancer Care Specialists of Illinois - Decatur
  - Dixon, Illinois, United States, 61021
    - Illinois CancerCare-Dixon
  - Effingham, Illinois, United States, 62401
    - Crossroads Cancer Center
  - Effingham, Illinois, United States, 62401
    - Carle Physician Group-Effingham
  - Eureka, Illinois, United States, 61530
    - Illinois CancerCare-Eureka
  - Galesburg, Illinois, United States, 61401
    - Western Illinois Cancer Treatment Center
  - Galesburg, Illinois, United States, 61401
    - Illinois CancerCare-Galesburg
  - Harvey, Illinois, United States, 60426
    - Ingalls Memorial Hospital
  - Kewanee, Illinois, United States, 61443
    - Illinois CancerCare-Kewanee Clinic
  - Macomb, Illinois, United States, 61455
    - Illinois CancerCare-Macomb
  - Mattoon, Illinois, United States, 61938
    - Carle Physician Group-Mattoon/Charleston
  - Mount Vernon, Illinois, United States, 62864
    - SSM Health Good Samaritan
  - O'Fallon, Illinois, United States, 62269
    - Cancer Care Center of O'Fallon
  - O'Fallon, Illinois, United States, 62269
    - HSHS Saint Elizabeth's Hospital
  - Ottawa, Illinois, United States, 61350
    - Illinois CancerCare-Ottawa Clinic
  - Pekin, Illinois, United States, 61554
    - Illinois CancerCare-Pekin
  - Pekin, Illinois, United States, 61554
    - OSF Saint Francis Radiation Oncology at Pekin
  - Peoria, Illinois, United States, 61636
    - Methodist Medical Center of Illinois
  - Peoria, Illinois, United States, 61637
    - OSF Saint Francis Medical Center
  - Peoria, Illinois, United States, 61615
    - Illinois CancerCare-Peoria
  - Peoria, Illinois, United States, 61615
    - OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  - Peru, Illinois, United States, 61354
    - Illinois CancerCare-Peru
  - Peru, Illinois, United States, 61354
    - Valley Radiation Oncology
  - Princeton, Illinois, United States, 61356
    - Illinois CancerCare-Princeton
  - Rockford, Illinois, United States, 61114
    - UW Health Carbone Cancer Center Rockford
  - Springfield, Illinois, United States, 62702
    - Southern Illinois University School of Medicine
  - Springfield, Illinois, United States, 62702
    - Springfield Clinic
  - Springfield, Illinois, United States, 62781
    - Springfield Memorial Hospital
  - Swansea, Illinois, United States, 62226
    - Southwest Illinois Health Services LLP
  - Urbana, Illinois, United States, 61801
    - Carle Cancer Center
  - Urbana, Illinois, United States, 61801
    - The Carle Foundation Hospital
  - Washington, Illinois, United States, 61571
    - Illinois CancerCare - Washington
- Indiana
  - Richmond, Indiana, United States, 47374
    - Reid Health
- Iowa
  - Carroll, Iowa, United States, 51401
    - Saint Anthony Regional Hospital
  - Clive, Iowa, United States, 50325
    - Mercy Cancer Center-West Lakes
  - Clive, Iowa, United States, 50325
    - UI Health Care Mission Cancer and Blood - West Des Moines Clinic
  - Council Bluffs, Iowa, United States, 51503
    - Alegent Health Mercy Hospital
  - Creston, Iowa, United States, 50801
    - Greater Regional Medical Center
  - Des Moines, Iowa, United States, 50309
    - Iowa Methodist Medical Center
  - Des Moines, Iowa, United States, 50314
    - Mercy Medical Center - Des Moines
  - Des Moines, Iowa, United States, 50314
    - Broadlawns Medical Center
  - Des Moines, Iowa, United States, 50316
    - Iowa Lutheran Hospital
  - Des Moines, Iowa, United States, 50309
    - UI Health Care Mission Cancer and Blood - Des Moines Clinic
  - Des Moines, Iowa, United States, 50314
    - UI Health Care Mission Cancer and Blood - Laurel Clinic
  - Fort Dodge, Iowa, United States, 50501
    - UI Healthcare Mission Cancer and Blood - Fort Dodge
  - West Des Moines, Iowa, United States, 50266-7700
    - Methodist West Hospital
  - West Des Moines, Iowa, United States, 50266
    - Mercy Medical Center-West Lakes
- Kansas
  - Garden City, Kansas, United States, 67846
    - Central Care Cancer Center - Garden City
  - Great Bend, Kansas, United States, 67530
    - Central Care Cancer Center - Great Bend
  - Kansas City, Kansas, United States, 66160
    - University of Kansas Cancer Center
  - Pittsburg, Kansas, United States, 66762
    - Mercy Hospital Pittsburg
  - Westwood, Kansas, United States, 66205
    - University of Kansas Hospital-Westwood Cancer Center
- Kentucky
  - Bardstown, Kentucky, United States, 40004
    - Flaget Memorial Hospital
  - Corbin, Kentucky, United States, 40701
    - Commonwealth Cancer Center-Corbin
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Radiation Oncology Resource Center
  - Lexington, Kentucky, United States, 40509
    - Saint Joseph Hospital East
  - Lexington, Kentucky, United States, 40504
    - Saint Joseph Hospital
  - London, Kentucky, United States, 40741
    - Saint Joseph London
  - Louisville, Kentucky, United States, 40202
    - Jewish Hospital
  - Louisville, Kentucky, United States, 40245
    - UofL Health Medical Center Northeast
  - Louisville, Kentucky, United States, 40215
    - Saints Mary and Elizabeth Hospital
  - Shepherdsville, Kentucky, United States, 40165
    - Jewish Hospital Medical Center South
- Louisiana
  - Baton Rouge, Louisiana, United States, 70805
    - LSU Health Baton Rouge-North Clinic
  - Baton Rouge, Louisiana, United States, 70809
    - Louisiana Hematology Oncology Associates LLC
  - Baton Rouge, Louisiana, United States, 70809
    - Mary Bird Perkins Cancer Center
  - Baton Rouge, Louisiana, United States, 70808
    - Our Lady of The Lake
  - Baton Rouge, Louisiana, United States, 70808
    - Our Lady of the Lake Physician Group
  - Covington, Louisiana, United States, 70433
    - Northshore Oncology Associates-Covington
  - Houma, Louisiana, United States, 70360
    - Terrebonne General Medical Center
  - Metairie, Louisiana, United States, 70006
    - East Jefferson General Hospital
  - Metairie, Louisiana, United States, 70006
    - LSU Healthcare Network / Metairie Multi-Specialty Clinic
  - Metairie, Louisiana, United States, 70002
    - Mary Bird Perkins Cancer Center - Metairie
  - New Orleans, Louisiana, United States, 70121
    - Ochsner Medical Center Jefferson
  - New Orleans, Louisiana, United States, 70112
    - University Medical Center New Orleans
  - New Orleans, Louisiana, United States, 70112
    - Louisiana State University Health Science Center
- Maryland
  - Baltimore, Maryland, United States, 21201
    - University of Maryland/Greenebaum Cancer Center
  - Baltimore, Maryland, United States, 21201
    - Maryland Proton Treatment Center
  - Columbia, Maryland, United States, 21044
    - Central Maryland Radiation Oncology in Howard County
  - Glen Burnie, Maryland, United States, 21061
    - UM Baltimore Washington Medical Center/Tate Cancer Center
- Massachusetts
  - Springfield, Massachusetts, United States, 01104
    - Mercy Medical Center
- Michigan
  - Alma, Michigan, United States, 48801
    - MyMichigan Medical Center Gratiot
  - Ann Arbor, Michigan, United States, 48106
    - Trinity Health Saint Joseph Mercy Hospital Ann Arbor
  - Brighton, Michigan, United States, 48114
    - Trinity Health IHA Medical Group Hematology Oncology - Brighton
  - Brighton, Michigan, United States, 48114
    - Trinity Health Medical Center - Brighton
  - Canton, Michigan, United States, 48188
    - Trinity Health IHA Medical Group Hematology Oncology - Canton
  - Canton, Michigan, United States, 48188
    - Trinity Health Medical Center - Canton
  - Caro, Michigan, United States, 48723
    - Caro Cancer Center
  - Chelsea, Michigan, United States, 48118
    - Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
  - Chelsea, Michigan, United States, 48118
    - Chelsea Hospital
  - Clarkston, Michigan, United States, 48346
    - Hematology Oncology Consultants-Clarkston
  - Clarkston, Michigan, United States, 48346
    - Newland Medical Associates-Clarkston
  - Detroit, Michigan, United States, 48236
    - Henry Ford Health Saint John Hospital
  - East China Township, Michigan, United States, 48054
    - Henry Ford River District Hospital
  - Flint, Michigan, United States, 48503
    - Hurley Medical Center
  - Flint, Michigan, United States, 48503
    - Genesee Hematology Oncology PC
  - Flint, Michigan, United States, 48503
    - Genesys Hurley Cancer Institute
  - Flint, Michigan, United States, 48503
    - Cancer Hematology Centers - Flint
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Henry Ford Saint John Hospital - Academic
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Henry Ford Saint John Hospital - Breast
  - Grosse Pointe Woods, Michigan, United States, 48236
    - Henry Ford Saint John Hospital - Van Elslander
  - Lansing, Michigan, United States, 48912
    - University of Michigan Health - Sparrow Lansing
  - Livonia, Michigan, United States, 48154
    - Trinity Health Saint Mary Mercy Livonia Hospital
  - Livonia, Michigan, United States, 48154
    - Hope Cancer Clinic
  - Macomb, Michigan, United States, 48044
    - Henry Ford Warren Hospital - Breast Macomb
  - Macomb, Michigan, United States, 48044
    - Henry Ford Saint John Hospital - Macomb Medical
  - Marlette, Michigan, United States, 48453
    - Saint Mary's Oncology/Hematology Associates of Marlette
  - Midland, Michigan, United States, 48670
    - MyMichigan Medical Center Midland
  - Pontiac, Michigan, United States, 48341
    - Hope Cancer Center
  - Pontiac, Michigan, United States, 48341
    - Newland Medical Associates-Pontiac
  - Pontiac, Michigan, United States, 48341
    - Trinity Health Saint Joseph Mercy Oakland Hospital
  - Pontiac, Michigan, United States, 48341
    - Michigan Healthcare Professionals Pontiac
  - Rochester Hills, Michigan, United States, 48309
    - Henry Ford Rochester Hospital
  - Saginaw, Michigan, United States, 48604
    - Oncology Hematology Associates of Saginaw Valley PC
  - Saginaw, Michigan, United States, 48601
    - MyMichigan Medical Center Saginaw
  - Sterling Heights, Michigan, United States, 48312
    - Bhadresh Nayak MD PC-Sterling Heights
  - Tawas City, Michigan, United States, 48764
    - MyMichigan Medical Center Tawas
  - Warren, Michigan, United States, 48088
    - Advanced Breast Care Center PLLC
  - Warren, Michigan, United States, 48093
    - Macomb Hematology Oncology PC
  - Warren, Michigan, United States, 48093
    - Henry Ford Madison Heights Hospital - Breast
  - Warren, Michigan, United States, 48093
    - Henry Ford Health Warren Hospital
  - Warren, Michigan, United States, 48093
    - Henry Ford Warren Hospital - GLCMS
  - West Branch, Michigan, United States, 48661
    - Saint Mary's Oncology/Hematology Associates of West Branch
  - Ypsilanti, Michigan, United States, 48197
    - Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
  - Ypsilanti, Michigan, United States, 48106
    - Huron Gastroenterology PC
- Minnesota
  - Bemidji, Minnesota, United States, 56601
    - Sanford Joe Lueken Cancer Center
  - Brainerd, Minnesota, United States, 56401
    - Essentia Health Saint Joseph's Medical Center
  - Burnsville, Minnesota, United States, 55337
    - Fairview Ridges Hospital
  - Burnsville, Minnesota, United States, 55337
    - Minnesota Oncology - Burnsville
  - Coon Rapids, Minnesota, United States, 55433
    - Mercy Hospital
  - Deer River, Minnesota, United States, 56636
    - Essentia Health - Deer River Clinic
  - Detroit Lakes, Minnesota, United States, 56501
    - Essentia Health Saint Mary's - Detroit Lakes Clinic
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Cancer Center
  - Duluth, Minnesota, United States, 55805
    - Essentia Health Saint Mary's Medical Center
  - Duluth, Minnesota, United States, 55805
    - Miller-Dwan Hospital
  - Edina, Minnesota, United States, 55435
    - Fairview Southdale Hospital
  - Fergus Falls, Minnesota, United States, 56537
    - Lake Region Healthcare Corporation-Cancer Care
  - Fosston, Minnesota, United States, 56542
    - Essentia Health - Fosston
  - Fridley, Minnesota, United States, 55432
    - Unity Hospital
  - Hibbing, Minnesota, United States, 55746
    - Essentia Health Hibbing Clinic
  - Maple Grove, Minnesota, United States, 55369
    - Fairview Clinics and Surgery Center Maple Grove
  - Maplewood, Minnesota, United States, 55109
    - Saint John's Hospital - Healtheast
  - Maplewood, Minnesota, United States, 55109
    - Minnesota Oncology Hematology PA-Maplewood
  - Minneapolis, Minnesota, United States, 55415
    - Hennepin County Medical Center
  - Minneapolis, Minnesota, United States, 55407
    - Abbott-Northwestern Hospital
  - Minneapolis, Minnesota, United States, 55454
    - Health Partners Inc
  - Monticello, Minnesota, United States, 55362
    - Monticello Cancer Center
  - New Ulm, Minnesota, United States, 56073
    - New Ulm Medical Center
  - Park Rapids, Minnesota, United States, 56470
    - Essentia Health - Park Rapids
  - Robbinsdale, Minnesota, United States, 55422
    - North Memorial Medical Health Center
  - Saint Cloud, Minnesota, United States, 56303
    - Coborn Cancer Center at Saint Cloud Hospital
  - Saint Louis Park, Minnesota, United States, 55416
    - Park Nicollet Clinic - Saint Louis Park
  - Saint Paul, Minnesota, United States, 55101
    - Regions Hospital
  - Saint Paul, Minnesota, United States, 55102
    - United Hospital
  - Sandstone, Minnesota, United States, 55072
    - Essentia Health Sandstone
  - Shakopee, Minnesota, United States, 55379
    - Saint Francis Regional Medical Center
  - Stillwater, Minnesota, United States, 55082
    - Lakeview Hospital
  - Thief River Falls, Minnesota, United States, 56701
    - Sanford Thief River Falls Medical Center
  - Virginia, Minnesota, United States, 55792
    - Essentia Health Virginia Clinic
  - Waconia, Minnesota, United States, 55387
    - Ridgeview Medical Center
  - Willmar, Minnesota, United States, 56201
    - Rice Memorial Hospital
  - Woodbury, Minnesota, United States, 55125
    - Minnesota Oncology Hematology PA-Woodbury
  - Worthington, Minnesota, United States, 56187
    - Sanford Cancer Center Worthington
  - Wyoming, Minnesota, United States, 55092
    - Fairview Lakes Medical Center
- Missouri
  - Ballwin, Missouri, United States, 63011
    - Mercy Oncology and Hematology - Clayton-Clarkson
  - Bolivar, Missouri, United States, 65613
    - Central Care Cancer Center - Bolivar
  - Bonne Terre, Missouri, United States, 63628
    - Parkland Health Center-Bonne Terre
  - Cape Girardeau, Missouri, United States, 63703
    - Saint Francis Medical Center
  - Cape Girardeau, Missouri, United States, 63703
    - Mercy Cancer Center - Cape Girardeau
  - Columbia, Missouri, United States, 65212
    - MU Health - University Hospital/Ellis Fischel Cancer Center
  - Creve Coeur, Missouri, United States, 63141
    - Siteman Cancer Center at West County Hospital
  - Farmington, Missouri, United States, 63640
    - Parkland Health Center - Farmington
  - Jefferson City, Missouri, United States, 65109
    - MU Health Care Goldschmidt Cancer Center
  - Joplin, Missouri, United States, 64804
    - Freeman Health System
  - Joplin, Missouri, United States, 64804
    - Mercy Hospital Joplin
  - Osage Beach, Missouri, United States, 65065
    - Lake Regional Hospital
  - Rolla, Missouri, United States, 65401
    - Mercy Clinic-Rolla-Cancer and Hematology
  - Rolla, Missouri, United States, 65401
    - Phelps Health Delbert Day Cancer Institute
  - Saint Joseph, Missouri, United States, 64506
    - Heartland Regional Medical Center
  - Sainte Genevieve, Missouri, United States, 63670
    - Sainte Genevieve County Memorial Hospital
  - Springfield, Missouri, United States, 65807
    - CoxHealth South Hospital
  - Springfield, Missouri, United States, 65804
    - Mercy Hospital Springfield
  - St Louis, Missouri, United States, 63110
    - Washington University School of Medicine
  - St Louis, Missouri, United States, 63129
    - Siteman Cancer Center-South County
  - St Louis, Missouri, United States, 63136
    - Siteman Cancer Center at Christian Hospital
  - St Louis, Missouri, United States, 63131
    - Missouri Baptist Medical Center
  - St Louis, Missouri, United States, 63141
    - Mercy Hospital Saint Louis
  - St Louis, Missouri, United States, 63128
    - Mercy Hospital South
  - Sullivan, Missouri, United States, 63080
    - Missouri Baptist Sullivan Hospital
  - Sunset Hills, Missouri, United States, 63127
    - BJC Outpatient Center at Sunset Hills
- Montana
  - Anaconda, Montana, United States, 59711
    - Community Hospital of Anaconda
  - Billings, Montana, United States, 59101
    - Billings Clinic Cancer Center
  - Bozeman, Montana, United States, 59715
    - Bozeman Health Deaconess Hospital
  - Great Falls, Montana, United States, 59405
    - Great Falls Clinic
  - Great Falls, Montana, United States, 59405
    - Benefis Sletten Cancer Institute
  - Havre, Montana, United States, 59501
    - Hi-Line Sletten Cancer Center
  - Helena, Montana, United States, 59601
    - Saint Peter's Community Hospital
  - Kalispell, Montana, United States, 59901
    - Logan Health Medical Center
  - Missoula, Montana, United States, 59804
    - Community Medical Center
- Nebraska
  - Grand Island, Nebraska, United States, 68803
    - Nebraska Cancer Specialists/Oncology Hematology West PC
  - Kearney, Nebraska, United States, 68847
    - CHI Health Good Samaritan
  - Kearney, Nebraska, United States, 68845
    - Fred and Pamela Buffett Cancer Center - Kearney
  - Lincoln, Nebraska, United States, 68510
    - Saint Elizabeth Regional Medical Center
  - Omaha, Nebraska, United States, 68124
    - Alegent Health Bergan Mercy Medical Center
  - Omaha, Nebraska, United States, 68122
    - Alegent Health Immanuel Medical Center
  - Omaha, Nebraska, United States, 68130
    - Alegent Health Lakeside Hospital
  - Omaha, Nebraska, United States, 68131
    - Creighton University Medical Center
  - Omaha, Nebraska, United States, 68122
    - Hematology and Oncology Consultants PC
  - Papillion, Nebraska, United States, 68046
    - Midlands Community Hospital
- New Jersey
  - Basking Ridge, New Jersey, United States, 07920
    - Memorial Sloan Kettering Basking Ridge
  - Englewood, New Jersey, United States, 07631
    - Englewood Hospital and Medical Center
  - Middletown, New Jersey, United States, 07748
    - Memorial Sloan Kettering Monmouth
  - Montvale, New Jersey, United States, 07645
    - Memorial Sloan Kettering Bergen
- New York
  - Buffalo, New York, United States, 14263
    - Roswell Park Cancer Institute
  - Commack, New York, United States, 11725
    - Memorial Sloan Kettering Commack
  - Harrison, New York, United States, 10604
    - Memorial Sloan Kettering Westchester
  - New York, New York, United States, 10065
    - Memorial Sloan Kettering Cancer Center
  - New York, New York, United States, 10065
    - NYP/Weill Cornell Medical Center
  - New York, New York, United States, 10016
    - Laura and Isaac Perlmutter Cancer Center at NYU Langone
  - Oswego, New York, United States, 13126
    - Upstate Cancer Center at Oswego
  - Oswego, New York, United States, 13126
    - Upstate Cancer Center Radiation Oncology at Oswego
  - Rochester, New York, United States, 14642
    - University of Rochester
  - Syracuse, New York, United States, 13210
    - State University of New York Upstate Medical University
  - Uniondale, New York, United States, 11553
    - Memorial Sloan Kettering Nassau
  - Verona, New York, United States, 13478
    - Upstate Cancer Center at Verona
- North Carolina
  - Clinton, North Carolina, United States, 28328
    - Southeastern Medical Oncology Center-Clinton
  - Goldsboro, North Carolina, United States, 27534
    - Southeastern Medical Oncology Center-Goldsboro
  - Goldsboro, North Carolina, United States, 27534
    - Wayne Memorial Hospital
  - Jacksonville, North Carolina, United States, 28546
    - Southeastern Medical Oncology Center-Jacksonville
  - Jacksonville, North Carolina, United States, 28546
    - Onslow Memorial Hospital
- North Dakota
  - Bismarck, North Dakota, United States, 58501
    - Sanford Bismarck Medical Center
  - Fargo, North Dakota, United States, 58122
    - Sanford Roger Maris Cancer Center
  - Fargo, North Dakota, United States, 58103
    - Essentia Health Cancer Center-South University Clinic
  - Fargo, North Dakota, United States, 58122
    - Sanford Broadway Medical Center
  - Fargo, North Dakota, United States, 58103
    - Sanford South University Medical Center
  - Fargo, North Dakota, United States, 58104
    - Sanford Medical Center Fargo
  - Jamestown, North Dakota, United States, 58401
    - Essentia Health - Jamestown Clinic
- Ohio
  - Beavercreek, Ohio, United States, 45431
    - Indu and Raj Soin Medical Center
  - Boardman, Ohio, United States, 44512
    - Saint Elizabeth Boardman Hospital
  - Centerville, Ohio, United States, 45459
    - Miami Valley Hospital South
  - Centerville, Ohio, United States, 45459
    - Dayton Physicians LLC-Miami Valley South
  - Cincinnati, Ohio, United States, 45220
    - Good Samaritan Hospital - Cincinnati
  - Cincinnati, Ohio, United States, 45242
    - Bethesda North Hospital
  - Cincinnati, Ohio, United States, 45236
    - Oncology Hematology Care Inc-Kenwood
  - Cincinnati, Ohio, United States, 45247
    - TriHealth Cancer Institute-Westside
  - Cincinnati, Ohio, United States, 45255
    - TriHealth Cancer Institute-Anderson
  - Cleveland, Ohio, United States, 44195
    - Cleveland Clinic Foundation
  - Columbus, Ohio, United States, 43210
    - Ohio State University Comprehensive Cancer Center
  - Dayton, Ohio, United States, 45406
    - Good Samaritan Hospital - Dayton
  - Dayton, Ohio, United States, 45409
    - Miami Valley Hospital
  - Dayton, Ohio, United States, 45415
    - Miami Valley Hospital North
  - Dayton, Ohio, United States, 45415
    - Dayton Physician LLC - Englewood
  - Dayton, Ohio, United States, 45409
    - Premier Blood and Cancer Center
  - Findlay, Ohio, United States, 45840
    - Blanchard Valley Hospital
  - Findlay, Ohio, United States, 45840
    - Armes Family Cancer Center
  - Findlay, Ohio, United States, 45840
    - Orion Cancer Care
  - Franklin, Ohio, United States, 45005-1066
    - Atrium Medical Center-Middletown Regional Hospital
  - Franklin, Ohio, United States, 45005
    - Dayton Physicians LLC-Atrium
  - Greenville, Ohio, United States, 45331
    - Wayne Hospital
  - Greenville, Ohio, United States, 45331
    - Dayton Physicians LLC-Wayne
  - Greenville, Ohio, United States, 45331
    - Miami Valley Cancer Care and Infusion
  - Kettering, Ohio, United States, 45429
    - Kettering Medical Center
  - Kettering, Ohio, United States, 45409
    - Greater Dayton Cancer Center
  - Kettering, Ohio, United States, 45420
    - First Dayton Cancer Care
  - Springfield, Ohio, United States, 45504
    - Springfield Regional Cancer Center
  - Springfield, Ohio, United States, 45504
    - Springfield Regional Medical Center
  - Troy, Ohio, United States, 45373
    - Upper Valley Medical Center
  - Troy, Ohio, United States, 45373
    - Dayton Physicians LLC - Troy
  - Warren, Ohio, United States, 44484
    - Saint Joseph Warren Hospital
  - Youngstown, Ohio, United States, 44501
    - Saint Elizabeth Youngstown Hospital
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma Health Sciences Center
  - Oklahoma City, Oklahoma, United States, 73120
    - Mercy Hospital Oklahoma City
  - Tulsa, Oklahoma, United States, 74146
    - Oklahoma Cancer Specialists and Research Institute-Tulsa
- Oregon
  - Baker City, Oregon, United States, 97814
    - Saint Alphonsus Cancer Care Center-Baker City
  - Ontario, Oregon, United States, 97914
    - Saint Alphonsus Cancer Care Center-Ontario
- Pennsylvania
  - Allentown, Pennsylvania, United States, 18103
    - Lehigh Valley Hospital-Cedar Crest
  - Bethlehem, Pennsylvania, United States, 18017
    - Lehigh Valley Hospital - Muhlenberg
  - Danville, Pennsylvania, United States, 17822
    - Geisinger Medical Center
  - East Stroudsburg, Pennsylvania, United States, 18301
    - Pocono Medical Center
  - Hazleton, Pennsylvania, United States, 18201
    - Geisinger Medical Center-Cancer Center Hazleton
  - Hazleton, Pennsylvania, United States, 18201
    - Lehigh Valley Hospital-Hazleton
  - Lewisburg, Pennsylvania, United States, 17837
    - Geisinger Medical Oncology-Lewisburg
  - Lewistown, Pennsylvania, United States, 17044
    - Lewistown Hospital
  - Pottsville, Pennsylvania, United States, 17901
    - Geisinger Cancer Services-Pottsville
  - Scranton, Pennsylvania, United States, 18510
    - Community Medical Center
  - Selinsgrove, Pennsylvania, United States, 17870
    - Geisinger Medical Oncology-Selinsgrove
  - Wilkes-Barre, Pennsylvania, United States, 18711
    - Geisinger Wyoming Valley/Henry Cancer Center
- Rhode Island
  - Providence, Rhode Island, United States, 02903
    - Rhode Island Hospital
- South Carolina
  - Boiling Springs, South Carolina, United States, 29316
    - Prisma Health Cancer Institute - Spartanburg
  - Charleston, South Carolina, United States, 29425
    - Medical University of South Carolina
  - Clinton, South Carolina, United States, 29325
    - Prisma Health Cancer Institute - Laurens
  - Easley, South Carolina, United States, 29640
    - Prisma Health Cancer Institute - Easley
  - Gaffney, South Carolina, United States, 29341
    - Gibbs Cancer Center-Gaffney
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Faris
  - Greenville, South Carolina, United States, 29615
    - Prisma Health Cancer Institute - Eastside
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Cancer Institute - Butternut
  - Greenville, South Carolina, United States, 29605
    - Prisma Health Greenville Memorial Hospital
  - Greer, South Carolina, United States, 29650
    - Prisma Health Cancer Institute - Greer
  - Greer, South Carolina, United States, 29651
    - Gibbs Cancer Center-Pelham
  - Seneca, South Carolina, United States, 29672
    - Prisma Health Cancer Institute - Seneca
  - Spartanburg, South Carolina, United States, 29303
    - Spartanburg Medical Center
  - Union, South Carolina, United States, 29379
    - SMC Center for Hematology Oncology Union
- South Dakota
  - Sioux Falls, South Dakota, United States, 57117-5134
    - Sanford USD Medical Center - Sioux Falls
  - Sioux Falls, South Dakota, United States, 57104
    - Sanford Cancer Center Oncology Clinic
- Tennessee
  - Chattanooga, Tennessee, United States, 37404
    - Memorial Hospital
  - Hixson, Tennessee, United States, 37343
    - Pulmonary Medicine Center of Chattanooga-Hixson
  - Ooltewah, Tennessee, United States, 37363
    - Memorial GYN Plus
- Texas
  - Bryan, Texas, United States, 77802
    - Saint Joseph Regional Cancer Center
  - Dallas, Texas, United States, 75235
    - Parkland Memorial Hospital
  - Dallas, Texas, United States, 75390
    - UT Southwestern/Simmons Cancer Center-Dallas
  - Dallas, Texas, United States, 75237
    - UT Southwestern Simmons Cancer Center - RedBird
  - Fort Worth, Texas, United States, 76104
    - UT Southwestern/Simmons Cancer Center-Fort Worth
  - Richardson, Texas, United States, 75080
    - UT Southwestern Clinical Center at Richardson/Plano
- Washington
  - Burien, Washington, United States, 98166
    - Highline Medical Center-Main Campus
  - Enumclaw, Washington, United States, 98022
    - Saint Elizabeth Hospital
  - Federal Way, Washington, United States, 98003
    - Saint Francis Hospital
  - Lakewood, Washington, United States, 98499
    - Saint Clare Hospital
  - Poulsbo, Washington, United States, 98370
    - Harrison HealthPartners Hematology and Oncology-Poulsbo
  - Silverdale, Washington, United States, 98383
    - Saint Michael Cancer Center
  - Tacoma, Washington, United States, 98405
    - Northwest Medical Specialties PLLC
  - Tacoma, Washington, United States, 98405
    - Franciscan Research Center-Northwest Medical Plaza
- West Virginia
  - Bridgeport, West Virginia, United States, 26330
    - United Hospital Center
  - Martinsburg, West Virginia, United States, 25401
    - WVUH-Berkely Medical Center
  - Morgantown, West Virginia, United States, 26506
    - West Virginia University Healthcare
  - Parkersburg, West Virginia, United States, 26101
    - Camden Clark Medical Center
- Wisconsin
  - Antigo, Wisconsin, United States, 54409
    - Langlade Hospital and Cancer Center
  - Ashland, Wisconsin, United States, 54806
    - Duluth Clinic Ashland
  - Ashland, Wisconsin, United States, 54806
    - Northwest Wisconsin Cancer Center
  - Eau Claire, Wisconsin, United States, 54701
    - Marshfield Medical Center-EC Cancer Center
  - Hayward, Wisconsin, United States, 54843
    - Essentia Health-Hayward Clinic
  - La Crosse, Wisconsin, United States, 54601
    - Gundersen Lutheran Medical Center
  - Ladysmith, Wisconsin, United States, 54848
    - Marshfield Medical Center - Ladysmith
  - Marshfield, Wisconsin, United States, 54449
    - Marshfield Medical Center-Marshfield
  - Medford, Wisconsin, United States, 54451
    - Aspirus Medford Hospital
  - Minocqua, Wisconsin, United States, 54548
    - Marshfield Medical Center - Minocqua
  - New Richmond, Wisconsin, United States, 54017
    - Cancer Center of Western Wisconsin
  - Rhinelander, Wisconsin, United States, 54501
    - Aspirus Cancer Care - James Beck Cancer Center
  - Rice Lake, Wisconsin, United States, 54868
    - Marshfield Medical Center-Rice Lake
  - Spooner, Wisconsin, United States, 54801
    - Essentia Health-Spooner Clinic
  - Stevens Point, Wisconsin, United States, 54482
    - Marshfield Medical Center-River Region at Stevens Point
  - Stevens Point, Wisconsin, United States, 54481
    - Aspirus Cancer Care - Stevens Point
  - Superior, Wisconsin, United States, 54880
    - Essentia Health Saint Mary's Hospital - Superior
  - Wausau, Wisconsin, United States, 54401
    - Aspirus Regional Cancer Center
  - Weston, Wisconsin, United States, 54476
    - Marshfield Medical Center - Weston
  - Wisconsin Rapids, Wisconsin, United States, 54494
    - Aspirus Cancer Care - Wisconsin Rapids
- Wyoming
  - Cheyenne, Wyoming, United States, 82001
    - Memorial Hospital of Laramie County
  - Cody, Wyoming, United States, 82414
    - Billings Clinic-Cody
  - Sheridan, Wyoming, United States, 82801
    - Welch Cancer Center

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

Description

Inclusion Criteria:

Step 1 Patient Registration Eligibility Criteria
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
Clinical stage T2-T4aN0/xM0 disease
Medically appropriate candidate for radical cystectomy as assessed by surgeon
No concomitant multifocal carcinoma in situ; a single focus is allowed
A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.
No clinical or radiographic evidence for locally advanced or metastatic disease
No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.
No prior radiation therapy to the bladder or prostate
No major surgery or radiation therapy =< 4 weeks of registration (TURBT is allowed).
Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Absolute neutrophil count (ANC) >= 1,000/mm^3
Platelet count >= 100,000/mm^3
Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard or investigator's discretion. The same formula should be used to calculate all subsequent creatinine clearances.
Total bilirubin =< 1.5 x upper limit of normal (ULN)
* (For patients with documented Gilbert's syndrome Total Bilirubin =< 3 x ULN)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
Alkaline phosphatase =< 2.5 x ULN
No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
No pre-existing sensory grade >= 2 neuropathy
No pre-existing grade >= 2 hearing loss
No serious intercurrent medical or psychiatric illness, including serious active infection
None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
Step 2 Patient Registration Eligibility Criteria
Patients must have completed 4 or more cycles of protocol-directed chemotherapy and DDR gene results must be available
Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
Cystoscopy and imaging performed to determine stage/treatment assignment

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: Non-Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (gemcitabine, cisplatin, bladder sparing) Participants receive gemcitabine hydrochloride IV over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim SC on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants with DDR gene alteration and disease stage < cT1 undergo bladder sparing.	Drug: Cisplatin Given IV Drug: Gemcitabine Hydrochloride Given IV Biological: Pegfilgrastim Given SC Procedure: Conventional Surgery Undergo bladder sparing
Experimental: Arm II (gemcitabine, cisplatin, cystectomy, chemoradiotherapy) Participants receive gemcitabine hydrochloride IV over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim SC on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants with DDR gene alteration and disease stage >= cT1 or participants without DDR gene alteration undergo radical cystectomy or chemoradiotherapy.	Drug: Cisplatin Given IV Drug: Gemcitabine Hydrochloride Given IV Biological: Pegfilgrastim Given SC Procedure: Radical Cystectomy Undergo radical cystectomy Other: Chemoradiotherapy Undergo chemoradiotherapy

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I (gemcitabine, cisplatin, bladder sparing)

Participants receive gemcitabine hydrochloride IV over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim SC on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants with DDR gene alteration and disease stage < cT1 undergo bladder sparing.

Drug: Cisplatin

Given IV

Drug: Gemcitabine Hydrochloride

Given IV

Biological: Pegfilgrastim

Given SC

Procedure: Conventional Surgery

Undergo bladder sparing

Experimental: Arm II (gemcitabine, cisplatin, cystectomy, chemoradiotherapy)

Drug: Cisplatin

Given IV

Drug: Gemcitabine Hydrochloride

Given IV

Biological: Pegfilgrastim

Given SC

Procedure: Radical Cystectomy

Undergo radical cystectomy

Other: Chemoradiotherapy

Undergo chemoradiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who are recurrence-free within the DDR mutated group who undergo the bladder sparing approach Time Frame: At 3 years	Will use Kaplan Meier survival analysis to estimate the proportion of patients who are recurrence-free at three years. Will use a one-sided 90% confidence interval.	At 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response rate for patients harboring deleterious DDR gene alterations Time Frame: After 6 courses (84 days)	Will be defined as the number of patients with less than a cT1 response divided by the total number of patients harboring deleterious DDR gene alterations who completed 6 cycles of dose dense gemcitabine and cisplatin.	After 6 courses (84 days)
Bladder-intact survival in DDR-altered patients with < cT1 responses who selected the bladder sparing approach Time Frame: Time from registration up to 5 years	Will be estimated with Kaplan-Meier estimators and corresponding 95% confidence intervals.	Time from registration up to 5 years
Overall survival Time Frame: Time from study registration up to 5 years	Will be estimated with Kaplan-Meier estimators and corresponding 95% confidence intervals.	Time from study registration up to 5 years
Pathologic response (pT0) rate at cystectomy in participants without DDR gene alterations Time Frame: Up to 5 years	This will be the number of patients without DDR gene alterations with pT0 at cystectomy divided by the number of patients without DDR gene alterations who underwent cystectomy following the completion of dose dense gemcitabine and cisplatin treatment. Will be estimated with a binomial point estimate and corresponding 95% binomial confidence intervals.	Up to 5 years
Recurrence-free survival Time Frame: Time from study registration up to 5 years	The Kaplan-Meier estimator will be used to estimate the proportion of patients who are recurrence-free success at three years under the two alternative definitions of recurrence-free success above. The point estimate for the three-year recurrence free survival rate will be reported with a 95% confidence interval. These analyses will also be repeated for 5-year recurrence free survival.	Time from study registration up to 5 years
The rate of cystectomies in patients with a DDR alteration and with a cT0/CIS/Ta response Time Frame: Within 3 years	Will be computed as the number of patients with a DDR alteration and with a cT0/CIS/Ta response who undergo a cystectomy within 3 years divided by the total number of patients with a DDR alteration and with a cT0/CIS/Ta response. Will be estimated with a binomial point estimate and corresponding 95% binomial confidence intervals.	Within 3 years
Proportion of patients in the bladder-sparing group who undergo local therapy Time Frame: Up to 5 years	Will be estimated with a binomial point estimate and 95% binomial confidence interval. The estimate will be determined as the number of patients who undergo local treatment (BCG or resection of non-invasive disease) in the bladder-sparing group divided by the total number of patients in the bladder-sparing group.	Up to 5 years

Collaborators and Investigators

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

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair: Gopa Iyer, MD, Memorial Sloan Kettering Cancer Center

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)

December 10, 2018

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2029

Study Registration Dates

First Submitted

July 25, 2018

First Submitted That Met QC Criteria

July 25, 2018

First Posted (Actual)

August 1, 2018

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

A031701
U10CA180821 (U.S. NIH Grant/Contract)
NCI-2018-01531 (Registry Identifier: NCI Clinical Trial Reporting Program)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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Head and Neck Squamous Cell Carcinoma

Bangladesh

Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations

A Phase II Study of Gemcitabine Plus Cisplatin Chemotherapy in Patients With Muscle-invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations

Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Collaborators

Investigators

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Estimated)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

Clinical Trials on Infiltrating Bladder Urothelial Carcinoma

Clinical Trials on Cisplatin

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations