Test de l'ajout du médicament anticancéreux, le cabozantinib, au traitement d'immunothérapie habituel, l'avelumab, chez des patients atteints d'un cancer urothélial métastatique, étude MAIN-CAV
MAIN-CAV : essai randomisé de phase III comparant le cabozantinib et l'avelumab d'entretien à l'avelumab d'entretien après une chimiothérapie à base de platine de première intention chez des patients atteints d'un cancer urothélial métastatique
This phase III trial compares the effect of adding cabozantinib to avelumab versus avelumab alone in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and avelumab together may further shrink the cancer or prevent it from returning/progressing.
Aperçu de l'étude
Statut
Les conditions
- Carcinome urothélial avancé de la vessie
- Carcinome urothélial avancé de l'uretère
- Carcinome urothélial de la vessie métastatique
- Carcinome urothélial métastatique du bassinet du rein
- Carcinome urothélial métastatique de l'uretère
- Carcinome urothélial urétral métastatique
- Cancer de la vessie de stade III AJCC v8
- Cancer du bassinet du rein de stade III AJCC v8
- Cancer de l'uretère de stade III AJCC v8
- Cancer de l'urètre de stade III AJCC v8
- Cancer de la vessie de stade IV AJCC v8
- Cancer du bassinet de stade IV AJCC v8
- Cancer de l'uretère de stade IV AJCC v8
- Cancer de l'urètre de stade IV AJCC v8
- Carcinome urothélial du bassinet du rein avancé
- Carcinome urothélial urétral avancé
- Cancer du bassinet du rein et de l'uretère de stade III AJCC v8
- Cancer du bassinet du rein et de l'uretère de stade IV AJCC v8
Description détaillée
PRIMARY OBJECTIVE:
I. To evaluate the effect of cabozantinib (cabozantinib S-malate) in combination with avelumab on overall survival (OS) compared to avelumab alone in patients with metastatic urothelial cancer (mUC) who did not progress during first-line platinum-based chemotherapy therapy, i.e. patients who had complete response (CR), partial response (PR) or stable disease (SD) after completion of first line platinum-based chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the effect of cabozantinib in combination with avelumab on progression-free survival (PFS) compared to avelumab alone for maintenance treatment following initial first-line treatment in patients who had a CR, PR or SD upon completion of first-line platinum-based chemotherapy.
II. To evaluate the safety and tolerability of cabozantinib in combination with avelumab in mUC compared to avelumab alone for maintenance treatment following initial first-line treatment in patients who had a CR, PR or SD upon completion of first-line platinum-based chemotherapy.
III. To evaluate activity of cabozantinib in combination with avelumab based on Response Evaluation Criteria in Solid Tumors (RECIST) compared to avelumab alone for maintenance treatment following initial first-line treatment in patients who had a CR, PR or SD upon completion of first-line platinum-based chemotherapy.
IV. Results of the primary analysis will be examined for consistency, while accounting for the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.
V. To evaluate the activity of cabozantinib in combination with avelumab compared to avelumab alone based on PD-L1 status of patients' tumors.
QUALITY OF LIFE (QOL) OBJECTIVES:
I. To compare quality-adjusted survival between patients randomized to receive cabozantinib and avelumab versus (vs.) avelumab alone using the European Quality of Life Five Dimension Five Level Scale Questionnaire (EQ-5D-5L).
II. To compare patient-reported fatigue as assessed by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue 4a from baseline through 12 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.
III. To compare patient-reported global health status/quality of life as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 from baseline through 12 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.
IV. To compare scale scores of the EORTC QLQ-Bladder Cancer Muscle-Invasive (BLM)30 (urinary symptoms, urostomy problems, catheter problems, future perspectives, abdominal bloating and flatulence, body image, sexual function) at 3, 6, 12, 18, and 24 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.
V. To compare scale scores of the EORTC QLQ-C30 (global health status/quality of life; physical, role, emotional, cognitive, and social function; symptoms) at 3, 6, 12, 18, and 24 months between patients randomized to receive cabozantinib and avelumab vs. avelumab alone.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive avelumab intravenously (IV) over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo computed tomography (CT) or magnetic resonance imaging (MRI) and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
ARM B: Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib orally (PO) daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated.
After completion of study treatment, patients are followed every 30 days through 90 days, then every 3 months for 5 years.
Type d'étude
Inscription (Estimé)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
- Cross Cancer Institute
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- University Health Network-Princess Margaret Hospital
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Saskatchewan
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Regina, Saskatchewan, Canada, S4T 7T1
- Allan Blair Cancer Centre
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Saskatoon, Saskatchewan, Canada, S7N 4H4
- Saskatoon Cancer Centre
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Arizona
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Phoenix, Arizona, États-Unis, 85054
- Mayo Clinic Hospital in Arizona
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California
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Auburn, California, États-Unis, 95602
- Sutter Auburn Faith Hospital
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Berkeley, California, États-Unis, 94704
- Alta Bates Summit Medical Center-Herrick Campus
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Fremont, California, États-Unis, 94538
- Palo Alto Medical Foundation-Fremont
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Modesto, California, États-Unis, 95355
- Memorial Medical Center
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Mountain View, California, États-Unis, 94040
- Palo Alto Medical Foundation-Camino Division
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Palo Alto, California, États-Unis, 94301
- Palo Alto Medical Foundation Health Care
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Roseville, California, États-Unis, 95661
- Sutter Roseville Medical Center
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Sacramento, California, États-Unis, 95816
- Sutter Medical Center Sacramento
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Sacramento, California, États-Unis, 95817
- University of California Davis Comprehensive Cancer Center
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San Francisco, California, États-Unis, 94115
- California Pacific Medical Center-Pacific Campus
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Santa Cruz, California, États-Unis, 95065
- Palo Alto Medical Foundation-Santa Cruz
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Sunnyvale, California, États-Unis, 94086
- Palo Alto Medical Foundation-Sunnyvale
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Vallejo, California, États-Unis, 94589
- Sutter Solano Medical Center/Cancer Center
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Delaware
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Millville, Delaware, États-Unis, 19967
- Beebe South Coastal Health Campus
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Newark, Delaware, États-Unis, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, États-Unis, 19713
- Medical Oncology Hematology Consultants PA
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Rehoboth Beach, Delaware, États-Unis, 19971
- Beebe Health Campus
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District of Columbia
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Washington D.C., District of Columbia, États-Unis, 20010
- MedStar Washington Hospital Center
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Florida
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Gainesville, Florida, États-Unis, 32610
- UF Health Cancer Institute - Gainesville
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Jacksonville, Florida, États-Unis, 32224-9980
- Mayo Clinic in Florida
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Weston, Florida, États-Unis, 33331
- Cleveland Clinic-Weston
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Illinois
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Aurora, Illinois, États-Unis, 60504
- Rush-Copley Medical Center
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Barrington, Illinois, États-Unis, 60010
- Advocate Good Shepherd Hospital
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Bloomington, Illinois, États-Unis, 61704
- Illinois CancerCare-Bloomington
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Canton, Illinois, États-Unis, 61520
- Illinois CancerCare-Canton
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Carthage, Illinois, États-Unis, 62321
- Illinois CancerCare-Carthage
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Centralia, Illinois, États-Unis, 62801
- Centralia Oncology Clinic
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Chicago, Illinois, États-Unis, 60611
- Northwestern University
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Chicago, Illinois, États-Unis, 60612
- University of Illinois
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Chicago, Illinois, États-Unis, 60657
- Advocate Illinois Masonic Medical Center
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Chicago, Illinois, États-Unis, 60612
- Rush MD Anderson Cancer Center
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Crystal Lake, Illinois, États-Unis, 60014
- AMG Crystal Lake - Oncology
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Danville, Illinois, États-Unis, 61832
- Carle at The Riverfront
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DeKalb, Illinois, États-Unis, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Decatur, Illinois, États-Unis, 62526
- Cancer Care Specialists of Illinois - Decatur
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Dixon, Illinois, États-Unis, 61021
- Illinois CancerCare-Dixon
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Downers Grove, Illinois, États-Unis, 60515
- Advocate Good Samaritan Hospital
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Effingham, Illinois, États-Unis, 62401
- Crossroads Cancer Center
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Effingham, Illinois, États-Unis, 62401
- Carle Physician Group-Effingham
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Elgin, Illinois, États-Unis, 60123
- Advocate Sherman Hospital
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Eureka, Illinois, États-Unis, 61530
- Illinois CancerCare-Eureka
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Galesburg, Illinois, États-Unis, 61401
- Illinois CancerCare-Galesburg
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Geneva, Illinois, États-Unis, 60134
- Northwestern Medicine Cancer Center Delnor
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Hazel Crest, Illinois, États-Unis, 60429
- Advocate South Suburban Hospital
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Kewanee, Illinois, États-Unis, 61443
- Illinois CancerCare-Kewanee Clinic
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Lake Forest, Illinois, États-Unis, 60045
- Northwestern Medicine Lake Forest Hospital
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Libertyville, Illinois, États-Unis, 60048
- Condell Memorial Hospital
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Libertyville, Illinois, États-Unis, 60048
- AMG Libertyville - Oncology
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Macomb, Illinois, États-Unis, 61455
- Illinois CancerCare-Macomb
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Mattoon, Illinois, États-Unis, 61938
- Carle Physician Group-Mattoon/Charleston
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O'Fallon, Illinois, États-Unis, 62269
- Cancer Care Center of O'Fallon
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Oak Lawn, Illinois, États-Unis, 60453-2699
- Advocate Christ Medical Center
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Ottawa, Illinois, États-Unis, 61350
- Illinois CancerCare-Ottawa Clinic
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Park Ridge, Illinois, États-Unis, 60068
- Advocate Lutheran General Hospital
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Pekin, Illinois, États-Unis, 61554
- Illinois CancerCare-Pekin
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Peoria, Illinois, États-Unis, 61615
- Illinois CancerCare-Peoria
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Peru, Illinois, États-Unis, 61354
- Illinois CancerCare-Peru
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Princeton, Illinois, États-Unis, 61356
- Illinois CancerCare-Princeton
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Rockford, Illinois, États-Unis, 61114
- UW Health Carbone Cancer Center Rockford
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Shiloh, Illinois, États-Unis, 62269
- Memorial Hospital East
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Springfield, Illinois, États-Unis, 62702
- Southern Illinois University School of Medicine
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Springfield, Illinois, États-Unis, 62702
- Springfield Clinic
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Springfield, Illinois, États-Unis, 62781
- Springfield Memorial Hospital
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Urbana, Illinois, États-Unis, 61801
- Carle Cancer Center
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Warrenville, Illinois, États-Unis, 60555
- Northwestern Medicine Cancer Center Warrenville
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Washington, Illinois, États-Unis, 61571
- Illinois CancerCare - Washington
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Yorkville, Illinois, États-Unis, 60560
- Rush-Copley Healthcare Center
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Indiana
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Crown Point, Indiana, États-Unis, 46307
- Northwest Cancer Center - Crown Point
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Dyer, Indiana, États-Unis, 46311
- Northwest Oncology LLC
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Hobart, Indiana, États-Unis, 46342
- Northwest Cancer Center - Hobart
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Hobart, Indiana, États-Unis, 46342
- Saint Mary Medical Center
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Indianapolis, Indiana, États-Unis, 46312
- Saint Catherine Hospital
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Munster, Indiana, États-Unis, 46321
- The Community Hospital
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Munster, Indiana, États-Unis, 46321
- Women's Diagnostic Center - Munster
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Valparaiso, Indiana, États-Unis, 46383
- Northwest Cancer Center - Valparaiso
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Iowa
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Ames, Iowa, États-Unis, 50010
- Mary Greeley Medical Center
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Ames, Iowa, États-Unis, 50010
- McFarland Clinic - Ames
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Boone, Iowa, États-Unis, 50036
- McFarland Clinic - Boone
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Fort Dodge, Iowa, États-Unis, 50501
- McFarland Clinic - Trinity Cancer Center
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Iowa City, Iowa, États-Unis, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Jefferson, Iowa, États-Unis, 50129
- McFarland Clinic - Jefferson
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Marshalltown, Iowa, États-Unis, 50158
- McFarland Clinic - Marshalltown
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Kentucky
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Louisville, Kentucky, États-Unis, 40207
- Baptist Health Louisville
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Maine
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Augusta, Maine, États-Unis, 04330
- Harold Alfond Center for Cancer Care
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Maryland
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Bethesda, Maryland, États-Unis, 20892
- National Institutes of Health Clinical Center
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Massachusetts
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Worcester, Massachusetts, États-Unis, 01655
- UMass Memorial Medical Center - University Campus
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Michigan
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Ann Arbor, Michigan, États-Unis, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Battle Creek, Michigan, États-Unis, 49017
- Bronson Battle Creek
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Brighton, Michigan, États-Unis, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Brighton, Michigan, États-Unis, 48114
- Trinity Health Medical Center - Brighton
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Canton, Michigan, États-Unis, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
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Canton, Michigan, États-Unis, 48188
- Trinity Health Medical Center - Canton
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Chelsea, Michigan, États-Unis, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Chelsea, Michigan, États-Unis, 48118
- Chelsea Hospital
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Clarkston, Michigan, États-Unis, 48346
- Hematology Oncology Consultants-Clarkston
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Clarkston, Michigan, États-Unis, 48346
- Newland Medical Associates-Clarkston
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Flint, Michigan, États-Unis, 48503
- Hurley Medical Center
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Flint, Michigan, États-Unis, 48503
- Genesee Hematology Oncology PC
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Flint, Michigan, États-Unis, 48503
- Genesys Hurley Cancer Institute
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Flint, Michigan, États-Unis, 48503
- Cancer Hematology Centers - Flint
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Grand Rapids, Michigan, États-Unis, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, États-Unis, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, États-Unis, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, États-Unis, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, États-Unis, 49009
- Beacon Kalamazoo Cancer Center
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Lansing, Michigan, États-Unis, 48912
- University of Michigan Health - Sparrow Lansing
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Livonia, Michigan, États-Unis, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
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Macomb, Michigan, États-Unis, 48044
- Henry Ford Saint John Hospital - Macomb Medical
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Muskegon, Michigan, États-Unis, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, États-Unis, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Pontiac, Michigan, États-Unis, 48341
- Hope Cancer Center
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Pontiac, Michigan, États-Unis, 48341
- Trinity Health Saint Joseph Mercy Oakland Hospital
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Pontiac, Michigan, États-Unis, 48341
- Michigan Healthcare Professionals Pontiac
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Pontiac, Michigan, États-Unis, 48341
- Trinity Health IHA Medical Group-Alice Gustafson Center
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Reed City, Michigan, États-Unis, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, États-Unis, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, États-Unis, 49684
- Munson Medical Center
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Wyoming, Michigan, États-Unis, 49519
- University of Michigan Health - West
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Ypsilanti, Michigan, États-Unis, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Ypsilanti, Michigan, États-Unis, 48106
- Huron Gastroenterology PC
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Minnesota
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Bemidji, Minnesota, États-Unis, 56601
- Sanford Joe Lueken Cancer Center
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Minneapolis, Minnesota, États-Unis, 55415
- Hennepin County Medical Center
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Minneapolis, Minnesota, États-Unis, 55407
- Abbott-Northwestern Hospital
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Rochester, Minnesota, États-Unis, 55905
- Mayo Clinic in Rochester
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Saint Cloud, Minnesota, États-Unis, 56303
- Coborn Cancer Center at Saint Cloud Hospital
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Saint Louis Park, Minnesota, États-Unis, 55416
- Park Nicollet Clinic - Saint Louis Park
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Saint Paul, Minnesota, États-Unis, 55101
- Regions Hospital
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Willmar, Minnesota, États-Unis, 56201
- Rice Memorial Hospital
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Missouri
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Cape Girardeau, Missouri, États-Unis, 63703
- Saint Francis Medical Center
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City of Saint Peters, Missouri, États-Unis, 63376
- Siteman Cancer Center at Saint Peters Hospital
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Columbia, Missouri, États-Unis, 65212
- MU Health - University Hospital/Ellis Fischel Cancer Center
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Creve Coeur, Missouri, États-Unis, 63141
- Siteman Cancer Center at West County Hospital
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Kansas City, Missouri, États-Unis, 64111
- Saint Luke's Hospital of Kansas City
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Lee's Summit, Missouri, États-Unis, 64086
- Saint Luke's East - Lee's Summit
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St Louis, Missouri, États-Unis, 63110
- Washington University School of Medicine
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St Louis, Missouri, États-Unis, 63129
- Siteman Cancer Center-South County
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St Louis, Missouri, États-Unis, 63136
- Siteman Cancer Center at Christian Hospital
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St Louis, Missouri, États-Unis, 63141
- Mercy Hospital Saint Louis
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Nevada
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Las Vegas, Nevada, États-Unis, 89102
- OptumCare Cancer Care at Charleston
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Las Vegas, Nevada, États-Unis, 89183
- OptumCare Cancer Care at Fort Apache
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New Hampshire
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Concord, New Hampshire, États-Unis, 03301
- New Hampshire Oncology Hematology PA-Concord
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Manchester, New Hampshire, États-Unis, 03103
- Solinsky Center for Cancer Care
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New Jersey
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Basking Ridge, New Jersey, États-Unis, 07920
- Memorial Sloan Kettering Basking Ridge
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Hackensack, New Jersey, États-Unis, 07601
- Hackensack University Medical Center
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Middletown, New Jersey, États-Unis, 07748
- Memorial Sloan Kettering Monmouth
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Montvale, New Jersey, États-Unis, 07645
- Memorial Sloan Kettering Bergen
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Morristown, New Jersey, États-Unis, 07960
- Morristown Medical Center
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Paterson, New Jersey, États-Unis, 07503
- Saint Joseph's Regional Medical Center
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Summit, New Jersey, États-Unis, 07902
- Overlook Hospital
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New Mexico
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Albuquerque, New Mexico, États-Unis, 87106
- University of New Mexico Cancer Center
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Las Cruces, New Mexico, États-Unis, 88011
- Memorial Medical Center-Las Cruces
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New York
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Commack, New York, États-Unis, 11725
- Memorial Sloan Kettering Commack
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Elmira, New York, États-Unis, 14905
- Arnot Ogden Medical Center/Falck Cancer Center
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Glens Falls, New York, États-Unis, 12801
- Glens Falls Hospital
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Harrison, New York, États-Unis, 10604
- Memorial Sloan Kettering Westchester
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New York, New York, États-Unis, 10065
- Memorial Sloan Kettering Cancer Center
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Oswego, New York, États-Unis, 13126
- Upstate Cancer Center at Oswego
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Stony Brook, New York, États-Unis, 11794
- Stony Brook University Medical Center
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Syracuse, New York, États-Unis, 13210
- State University of New York Upstate Medical University
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Syracuse, New York, États-Unis, 13215
- SUNY Upstate Medical Center-Community Campus
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Uniondale, New York, États-Unis, 11553
- Memorial Sloan Kettering Nassau
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Verona, New York, États-Unis, 13478
- Upstate Cancer Center at Verona
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North Carolina
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Charlotte, North Carolina, États-Unis, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Charlotte, North Carolina, États-Unis, 28262
- Atrium Health University City/LCI-University
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Charlotte, North Carolina, États-Unis, 28211
- Levine Cancer Institute-SouthPark
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Charlotte, North Carolina, États-Unis, 28277
- Levine Cancer Institute-Ballantyne
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Clinton, North Carolina, États-Unis, 28328
- Southeastern Medical Oncology Center-Clinton
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Concord, North Carolina, États-Unis, 28025
- Atrium Health Cabarrus/LCI-Concord
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Goldsboro, North Carolina, États-Unis, 27534
- Southeastern Medical Oncology Center-Goldsboro
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Jacksonville, North Carolina, États-Unis, 28546
- Southeastern Medical Oncology Center-Jacksonville
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Lincolnton, North Carolina, États-Unis, 28092
- Atrium Health Lincoln/LCI-Lincolnton
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Shelby, North Carolina, États-Unis, 28150
- Atrium Health Cleveland/LCI-Cleveland
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Winston-Salem, North Carolina, États-Unis, 27157
- Wake Forest University Health Sciences
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North Dakota
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Bismarck, North Dakota, États-Unis, 58501
- Sanford Bismarck Medical Center
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Fargo, North Dakota, États-Unis, 58122
- Sanford Roger Maris Cancer Center
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Fargo, North Dakota, États-Unis, 58122
- Sanford Broadway Medical Center
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Ohio
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Akron, Ohio, États-Unis, 44307
- Cleveland Clinic Akron General
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Centerville, Ohio, États-Unis, 45459
- Miami Valley Hospital South
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Cleveland, Ohio, États-Unis, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, États-Unis, 44111
- Cleveland Clinic Cancer Center/Fairview Hospital
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Dayton, Ohio, États-Unis, 45415
- Miami Valley Hospital North
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Dayton, Ohio, États-Unis, 45415
- Dayton Physician LLC - Englewood
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Dayton, Ohio, États-Unis, 45409
- Premier Blood and Cancer Center
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Franklin, Ohio, États-Unis, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Greenville, Ohio, États-Unis, 45331
- Miami Valley Cancer Care and Infusion
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Kettering, Ohio, États-Unis, 45429
- Kettering Medical Center
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Mansfield, Ohio, États-Unis, 44906
- Cleveland Clinic Cancer Center Mansfield
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Mayfield Heights, Ohio, États-Unis, 44124
- Hillcrest Hospital Cancer Center
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Sandusky, Ohio, États-Unis, 44870
- North Coast Cancer Care
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Strongsville, Ohio, États-Unis, 44136
- Cleveland Clinic Cancer Center Strongsville
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Toledo, Ohio, États-Unis, 43623
- Toledo Clinic Cancer Centers-Toledo
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Troy, Ohio, États-Unis, 45373
- Upper Valley Medical Center
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Warrensville Heights, Ohio, États-Unis, 44122
- South Pointe Hospital
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Wooster, Ohio, États-Unis, 44691
- Cleveland Clinic Wooster Family Health and Surgery Center
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis, 73104
- University of Oklahoma Health Sciences Center
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Tulsa, Oklahoma, États-Unis, 74146
- Oklahoma Cancer Specialists and Research Institute-Tulsa
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Oregon
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Gresham, Oregon, États-Unis, 97030
- Legacy Mount Hood Medical Center
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Portland, Oregon, États-Unis, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Tualatin, Oregon, États-Unis, 97062
- Legacy Meridian Park Hospital
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Pennsylvania
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Allentown, Pennsylvania, États-Unis, 18103
- Lehigh Valley Hospital-Cedar Crest
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Bethlehem, Pennsylvania, États-Unis, 18017
- Lehigh Valley Hospital - Muhlenberg
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Harrisburg, Pennsylvania, États-Unis, 17111
- Penn State Health Medical Group - Andrews Patel Hematology/Oncology East
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Hershey, Pennsylvania, États-Unis, 17033-0850
- Penn State Milton S Hershey Medical Center
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Philadelphia, Pennsylvania, États-Unis, 19107
- Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, États-Unis, 19148
- Jefferson Methodist Hospital
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South Carolina
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Boiling Springs, South Carolina, États-Unis, 29316
- Prisma Health Cancer Institute - Spartanburg
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Charleston, South Carolina, États-Unis, 29425
- Medical University of South Carolina
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Easley, South Carolina, États-Unis, 29640
- Prisma Health Cancer Institute - Easley
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Greenville, South Carolina, États-Unis, 29605
- Prisma Health Cancer Institute - Faris
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Greenville, South Carolina, États-Unis, 29615
- Prisma Health Cancer Institute - Eastside
-
Greenville, South Carolina, États-Unis, 29605
- Prisma Health Cancer Institute - Butternut
-
Greenville, South Carolina, États-Unis, 29605
- Prisma Health Greenville Memorial Hospital
-
Greer, South Carolina, États-Unis, 29650
- Prisma Health Cancer Institute - Greer
-
Rock Hill, South Carolina, États-Unis, 29732
- Levine Cancer Institute-Rock Hill
-
Seneca, South Carolina, États-Unis, 29672
- Prisma Health Cancer Institute - Seneca
-
-
South Dakota
-
Aberdeen, South Dakota, États-Unis, 57401
- Avera Cancer Institute-Aberdeen
-
Rapid City, South Dakota, États-Unis, 57701
- Rapid City Regional Hospital
-
Sioux Falls, South Dakota, États-Unis, 57105
- Avera Cancer Institute
-
Sioux Falls, South Dakota, États-Unis, 57117-5134
- Sanford USD Medical Center - Sioux Falls
-
Sioux Falls, South Dakota, États-Unis, 57104
- Sanford Cancer Center Oncology Clinic
-
Yankton, South Dakota, États-Unis, 57078
- Avera Cancer Institute at Yankton
-
-
Tennessee
-
Alcoa, Tennessee, États-Unis, 37701
- University Cancer Specialists - Alcoa
-
Knoxville, Tennessee, États-Unis, 37920
- University of Tennessee - Knoxville
-
-
Texas
-
Dallas, Texas, États-Unis, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Dallas, Texas, États-Unis, 75237
- UT Southwestern Simmons Cancer Center - RedBird
-
Fort Worth, Texas, États-Unis, 76104
- UT Southwestern/Simmons Cancer Center-Fort Worth
-
Richardson, Texas, États-Unis, 75080
- UT Southwestern Clinical Center at Richardson/Plano
-
-
Virginia
-
Mechanicsville, Virginia, États-Unis, 23116
- Bon Secours Memorial Regional Medical Center
-
Midlothian, Virginia, États-Unis, 23114
- Bon Secours Saint Francis Medical Center
-
Richmond, Virginia, États-Unis, 23235
- VCU Massey Cancer Center at Stony Point
-
Richmond, Virginia, États-Unis, 23229
- Virginia Cancer Institute
-
Richmond, Virginia, États-Unis, 23226
- Bon Secours Saint Mary's Hospital
-
Richmond, Virginia, États-Unis, 23298
- VCU Massey Comprehensive Cancer Center
-
South Hill, Virginia, États-Unis, 23970
- VCU Community Memorial Health Center
-
Winchester, Virginia, États-Unis, 22601
- Shenandoah Oncology PC
-
-
Washington
-
Renton, Washington, États-Unis, 98055
- Valley Medical Center
-
Vancouver, Washington, États-Unis, 98686
- Legacy Salmon Creek Hospital
-
Vancouver, Washington, États-Unis, 98684
- Legacy Cancer Institute Medical Oncology and Day Treatment
-
-
West Virginia
-
Charleston, West Virginia, États-Unis, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
-
-
Wisconsin
-
Burlington, Wisconsin, États-Unis, 53105
- Aurora Cancer Care-Southern Lakes VLCC
-
Eau Claire, Wisconsin, États-Unis, 54701
- Marshfield Medical Center-EC Cancer Center
-
Germantown, Wisconsin, États-Unis, 53022
- Aurora Health Care Germantown Health Center
-
Grafton, Wisconsin, États-Unis, 53024
- Aurora Cancer Care-Grafton
-
Green Bay, Wisconsin, États-Unis, 54311
- Aurora BayCare Medical Center
-
Kenosha, Wisconsin, États-Unis, 53142
- Aurora Cancer Care-Kenosha South
-
Marinette, Wisconsin, États-Unis, 54143
- Aurora Bay Area Medical Group-Marinette
-
Marshfield, Wisconsin, États-Unis, 54449
- Marshfield Medical Center-Marshfield
-
Menomonee Falls, Wisconsin, États-Unis, 53051
- Froedtert Menomonee Falls Hospital
-
Milwaukee, Wisconsin, États-Unis, 53226
- Medical College of Wisconsin
-
Milwaukee, Wisconsin, États-Unis, 53209
- Aurora Cancer Care-Milwaukee
-
Milwaukee, Wisconsin, États-Unis, 53215
- Aurora Saint Luke's Medical Center
-
Milwaukee, Wisconsin, États-Unis, 53233
- Aurora Sinai Medical Center
-
Minocqua, Wisconsin, États-Unis, 54548
- Marshfield Medical Center - Minocqua
-
Mukwonago, Wisconsin, États-Unis, 53149
- ProHealth D N Greenwald Center
-
New Richmond, Wisconsin, États-Unis, 54017
- Cancer Center of Western Wisconsin
-
Oak Creek, Wisconsin, États-Unis, 53154
- Drexel Town Square Health Center
-
Oconomowoc, Wisconsin, États-Unis, 53066
- ProHealth Oconomowoc Memorial Hospital
-
Oshkosh, Wisconsin, États-Unis, 54904
- Vince Lombardi Cancer Clinic - Oshkosh
-
Racine, Wisconsin, États-Unis, 53406
- Aurora Cancer Care-Racine
-
Rice Lake, Wisconsin, États-Unis, 54868
- Marshfield Medical Center-Rice Lake
-
Sheboygan, Wisconsin, États-Unis, 53081
- Vince Lombardi Cancer Clinic-Sheboygan
-
Stevens Point, Wisconsin, États-Unis, 54482
- Marshfield Medical Center-River Region at Stevens Point
-
Summit, Wisconsin, États-Unis, 53066
- Aurora Medical Center in Summit
-
Two Rivers, Wisconsin, États-Unis, 54241
- Vince Lombardi Cancer Clinic-Two Rivers
-
Waukesha, Wisconsin, États-Unis, 53188
- UW Cancer Center at ProHealth Care
-
Waukesha, Wisconsin, États-Unis, 53188
- ProHealth Waukesha Memorial Hospital
-
Wauwatosa, Wisconsin, États-Unis, 53226
- Aurora Cancer Care-Milwaukee West
-
West Allis, Wisconsin, États-Unis, 53227
- Aurora West Allis Medical Center
-
West Bend, Wisconsin, États-Unis, 53095
- Froedtert West Bend Hospital/Kraemer Cancer Center
-
Weston, Wisconsin, États-Unis, 54476
- Marshfield Medical Center - Weston
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
-
Histologically or cytologically-confirmed diagnosis of advanced or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies except for small-cell histology), including N3 only disease prior to start of first-line platinum-based chemotherapy
-
Prior first-line treatment must have consisted of 4-6 cycles of 1st-line therapy (platinum-based chemotherapy; gemcitabine-cisplatin, gemcitabine-carboplatin, methotrexate, vinblastine, doxorubicin and cisplatin [MVAC] or dose-dense [dd]MVAC)
-
No more than 1 line of prior chemotherapy for metastatic or locally advanced disease (neoadjuvant or adjuvant chemotherapy will be allowed if given 12 or more months prior to registration)
-
Tumor objective response of CR, PR, or SD upon completion of first line platinum-based chemotherapy by treating physician's assessment
-
The last dose of first-line chemotherapy must have been received no less than 3 weeks, and no more than 10 weeks, prior to randomization in the present study
-
No prior immunotherapy with IL-2, IFN-alpha, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
-
Age >= 18 years
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
-
Women of childbearing potential must have a negative pregnancy test =< 14 days prior to registration.
- Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
-
No use of immunosuppressive medication within 7 days prior to randomization except:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection);
- Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent;
- Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
-
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
-
Patients with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible
-
None of the following:
-
Active autoimmune disease that might deteriorate when receiving the anti PD-L1 agent, avelumab.
-
No known symptomatic central nervous system (CNS) metastases. Patients with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to randomization, have discontinued corticosteroid treatment for at least 2 weeks, and are neurologically stable. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.
-
No major surgery within 4 weeks prior to randomization. Subjects must have complete wound healing from surgery before randomization. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
-
No palliative radiotherapy within 48 hours prior to patient randomization.
-
No hemoptysis of ≥ 0.5 teaspoon (2.5 mL) of red blood, clinically significant hematuria, hematemesis, coagulopathy, or other history of significant bleeding (eg. Pulmonary hemorrhage) within 3 months before randomization.
-
No known cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
-
No administration of a live, attenuated vaccine within 30 days prior to randomization. The use of inactivated (killed) vaccines for the prevention of infectious disease is permitted. The use of COVID-19 vaccines is permitted.
-
No uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
-
Cardiovascular disorders including:
- Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
- Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
- The patient has a known history of corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms and confirmed by electrocardiogram (ECG) within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
- Any history of congenital long QT syndrome.
- Stroke, transient ischemic attack (TIA), myocardial infarction, or other symptomatic ischemic event or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism [DVT/PE]) within 6 months before randomization. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if asymptomatic and stable at screening and treated with low molecular weight heparin (LMWH) or the direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban for at least 1 week before randomization. Non-symptomatic white matter disease in the brain is acceptable.
-
No significant gastrointestinal disorders, particularly those associated with a high risk of perforation or fistula formation including unresolved active peptic ulcer disease, cholecystitis, diverticultis, symptomatic cholangitis or appendicitis, or malabsorption syndrome within 28 days of randomization.
-
No other clinically significant disorders such as:
- Any active infection requiring systemic treatment within 14 days before randomization. Subjects receiving oral (including prophylactic) antibiotics with no symptoms of infection at randomization are eligible.
- Serious non-healing wound/ulcer/bone fracture within 28 days before randomization
- History of organ or allogeneic stem cell transplant
-
No persisting toxicity related to prior therapy grade > 2 constituting a safety risk based on the investigator's judgment.
-
No diagnosis of any other malignancy within 3 years prior to randomization, except for locally curable cancers that have been adequately treated such as basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, Gleason < 7 prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration), or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms and no indication for treatment.
-
No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel).
-
Allowed anticoagulants are the following:
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
-
-
-
-
Absolute neutrophil count (ANC) >= 1,000/mm^3
-
Platelet count >= 100,000/mm^3
-
Hemoglobin >= 8 g/dL
-
Calculated (Calc.) creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
-
Total serum bilirubin =< 1.5 x upper limit of normal (ULN)
-
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)
-
Urine protein creatinine (UPC) ratio =< 1 or 24-hour protein < 1 g
-
Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
- Psychiatric illness which would prevent the patient from giving informed consent.
- Uncontrolled medical conditions which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
- Patients who cannot swallow oral formulations of the agent(s).
In addition:
- Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom).
- Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and or steroids equivalent to < 10 mg prednisone daily, not on immunosuppressive medications and patients with positive serology are eligible. Patients with vitiligo, endocrine deficiencies including hypo or hyper thyroid disease managed with replacement, diabetes type 1 are eligible.
- Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the study and continue for 4 months after the last dose of study drugs, even if oral contraceptives are also used.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur actif: Arm A (avelumab)
Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated. |
Ancillary studies
Autres noms:
Undergo CT
Autres noms:
Undergo MRI
Autres noms:
Ancillary studies Undergo bone scan
Autres noms:
Given IV
Autres noms:
Undergo collection of blood and urine samples
Autres noms:
|
|
Expérimental: Arm B (avelumab, cabozantinib)
Patients receive avelumab IV over 60 minutes on days 1 and 15 of each cycle and cabozantinib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo bone scan at screening and undergo CT or MRI and biospecimen collection throughout the trial. Patients may undergo urine sample collection as clinically indicated. |
Ancillary studies
Autres noms:
Undergo CT
Autres noms:
Undergo MRI
Autres noms:
Ancillary studies Given PO
Autres noms:
Undergo bone scan
Autres noms:
Given IV
Autres noms:
Undergo collection of blood and urine samples
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Overall survival (OS)
Délai: Time from randomization until death due to any cause, assessed up to 5 years
|
Subgroup analyses will be done using a stratified Cox model that includes the treatment arm assignment as an explanatory variable and a separate model will be generated for each level for the subgroup of interest. |
Time from randomization until death due to any cause, assessed up to 5 years
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Progression free survival (PFS)
Délai: Time from randomization until disease progression as assessed by the treating physician using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, assessed up to 5 years
|
A stratified Cox model will be used to compare the outcomes between the two treatment groups. The subgroup analyses will be done using a stratified Cox model that includes the treatment arm assignment as an explanatory variable and a separate model will be generated for each level for the subgroup of interest. |
Time from randomization until disease progression as assessed by the treating physician using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, assessed up to 5 years
|
|
Tumor response
Délai: Up to 5 years
|
Will be defined as a complete response or partial response (PR) as measured with Immune-Modified RECIST. Will be compared between the arms using a Mantel-Haenszel test (that accounts for the randomization stratification factors) comparing the response rates between the two treatment arms. This analysis will only include patients who had a PR or stable disease (SD) response to first-line therapy. An additional analysis will be conducted using logistic regression analysis that includes treatment arm and any baseline variables that are imbalanced between the arms as explanatory variable. |
Up to 5 years
|
|
Incidence of adverse events (AE)
Délai: Up to 5 years
|
Will be assessed by Common Terminology Criteria for Adverse Events 5.0. Will be summarized with frequencies and relative frequencies. The maximum grade for an AE will be recorded for each patient by treatment arm. The number (percent) of patients that experience each observed adverse event will be summarized by treatment arm. In addition, the proportion of patients that experience a grade 3+, grade 4+, and grade 5 adverse event will be summarized as the number and percent of patients by treatment arm. The primary summary will be regardless of attribution. Will also do an analogous summary for the adverse events that were deemed at least possibly related to treatment. |
Up to 5 years
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Shilpa Gupta, Alliance for Clinical Trials in Oncology
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies urogénitales
- Tumeurs urogénitales
- Tumeurs par site
- Tumeurs
- Maladies urogénitales masculines
- Maladies urologiques
- Maladies urogénitales féminines
- Maladies urogénitales féminines et complications de la grossesse
- Tumeurs urologiques
- Maladies urétérales
- Maladies de la vessie urinaire
- Maladies urétrales
- Tumeurs urétérales
- Tumeurs de la vessie urinaire
- Tumeurs urétrales
- Techniques d'investigation
- Techniques de laboratoire clinique
- Techniques et procédures de diagnostic
- Diagnostic
- Techniques de chimie, analytique
- Analyse du spectre
- Manipulation des échantillons
- Spectroscopie de résonance magnétique
- coulumab
- cabozantinib
Autres numéros d'identification d'étude
- NCI-2021-11166
- U10CA180821 (Subvention/contrat des NIH des États-Unis)
- NCI-2021-11166 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- A032001 (Autre identifiant: CTEP)
- A032001 (Autre identifiant: Alliance for Clinical Trials in Oncology)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
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
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .