AzTrials
AzTrials

Advanced Bladder Urothelial CarcinomaPhase 3NCT05092958

Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study

A Phase 3 study testing Avelumab, Biospecimen Collection and Bone Scan in people with Advanced Bladder Urothelial Carcinoma and Advanced Renal Pelvis Urothelial Carcinoma, run by National Cancer Institute (NCI) at 275 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Avelumab, Biospecimen Collection and Bone Scan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
654 participants
Where
275 sitesin 2 countries
Study dates
3 Jun 2022to 15 Jul 2029
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

None listed.

Trial locations and contacts

275 sites in 2 countries.

275 sites in 2 countries

United States271 sites

  • Avera Cancer Institute-Aberdeen

    Aberdeen, South Dakota, 57401

  • Cleveland Clinic Akron General

    Akron, Ohio, 44307

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • University Cancer Specialists - Alcoa

    Alcoa, Tennessee, 37701

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Advocate Good Shepherd Hospital

    Barrington, Illinois, 60010

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Vandalia Health/CAMC Institute for Academic Medicine

    Charleston, West Virginia, 25304

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Levine Cancer Institute-SouthPark

    Charlotte, North Carolina, 28211

  • Atrium Health University City/LCI-University

    Charlotte, North Carolina, 28262

  • Levine Cancer Institute-Ballantyne

    Charlotte, North Carolina, 28277

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • MU Health - University Hospital/Ellis Fischel Cancer Center

    Columbia, Missouri, 65212

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Atrium Health Cabarrus/LCI-Concord

    Concord, North Carolina, 28025

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Northwest Cancer Center - Crown Point

    Crown Point, Indiana, 46307

  • AMG Crystal Lake - Oncology

    Crystal Lake, Illinois, 60014

  • UT Southwestern Simmons Cancer Center - RedBird

    Dallas, Texas, 75237

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Premier Blood and Cancer Center

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Illinois CancerCare-Dixon

    Dixon, Illinois, 61021

  • Advocate Good Samaritan Hospital

    Downers Grove, Illinois, 60515

  • Northwest Oncology LLC

    Dyer, Indiana, 46311

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Advocate Sherman Hospital

    Elgin, Illinois, 60123

  • Arnot Ogden Medical Center/Falck Cancer Center

    Elmira, New York, 14905

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Palo Alto Medical Foundation-Fremont

    Fremont, California, 94538

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • Southeastern Medical Oncology Center-Goldsboro

    Goldsboro, North Carolina, 27534

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Miami Valley Cancer Care and Infusion

    Greenville, Ohio, 45331

  • Prisma Health Cancer Institute - Butternut

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Legacy Mount Hood Medical Center

    Gresham, Oregon, 97030

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Penn State Health Medical Group - Andrews Patel Hematology/Oncology East

    Harrisburg, Pennsylvania, 17111

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Advocate South Suburban Hospital

    Hazel Crest, Illinois, 60429

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Northwest Cancer Center - Hobart

    Hobart, Indiana, 46342

  • Saint Mary Medical Center

    Hobart, Indiana, 46342

  • Saint Catherine Hospital

    Indianapolis, Indiana, 46312

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Southeastern Medical Oncology Center-Jacksonville

    Jacksonville, North Carolina, 28546

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Beacon Kalamazoo Cancer Center

    Kalamazoo, Michigan, 49009

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37920

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • Memorial Medical Center-Las Cruces

    Las Cruces, New Mexico, 88011

  • OptumCare Cancer Care at Charleston

    Las Vegas, Nevada, 89102

  • OptumCare Cancer Care at Fort Apache

    Las Vegas, Nevada, 89183

  • Saint Luke's East - Lee's Summit

    Lee's Summit, Missouri, 64086

  • AMG Libertyville - Oncology

    Libertyville, Illinois, 60048

  • Condell Memorial Hospital

    Libertyville, Illinois, 60048

  • Atrium Health Lincoln/LCI-Lincolnton

    Lincolnton, North Carolina, 28092

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Baptist Health Louisville

    Louisville, Kentucky, 40207

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Henry Ford Saint John Hospital - Macomb Medical

    Macomb, Michigan, 48044

  • Solinsky Center for Cancer Care

    Manchester, New Hampshire, 03103

  • Cleveland Clinic Cancer Center Mansfield

    Mansfield, Ohio, 44906

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • McFarland Clinic - Marshalltown

    Marshalltown, Iowa, 50158

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Bon Secours Memorial Regional Medical Center

    Mechanicsville, Virginia, 23116

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Bon Secours Saint Francis Medical Center

    Midlothian, Virginia, 23114

  • Beebe South Coastal Health Campus

    Millville, Delaware, 19967

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • Memorial Medical Center

    Modesto, California, 95355

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • The Community Hospital

    Munster, Indiana, 46321

  • Women's Diagnostic Center - Munster

    Munster, Indiana, 46321

  • Trinity Health Muskegon Hospital

    Muskegon, Michigan, 49444

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Cancer and Hematology Centers of Western Michigan - Norton Shores

    Norton Shores, Michigan, 49444

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • Drexel Town Square Health Center

    Oak Creek, Wisconsin, 53154

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453-2699

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Vince Lombardi Cancer Clinic - Oshkosh

    Oshkosh, Wisconsin, 54904

  • Upstate Cancer Center at Oswego

    Oswego, New York, 13126

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Jefferson Methodist Hospital

    Philadelphia, Pennsylvania, 19148

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Hope Cancer Center

    Pontiac, Michigan, 48341

  • Michigan Healthcare Professionals Pontiac

    Pontiac, Michigan, 48341

  • Newland Medical Associates-Pontiac

    Pontiac, Michigan, 48341

  • Trinity Health Saint Joseph Mercy Oakland Hospital

    Pontiac, Michigan, 48341

  • Legacy Good Samaritan Hospital and Medical Center

    Portland, Oregon, 97210

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Aurora Cancer Care-Racine

    Racine, Wisconsin, 53406

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Corewell Health Reed City Hospital

    Reed City, Michigan, 49677

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Valley Medical Center

    Renton, Washington, 98055

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • UT Southwestern Clinical Center at Richardson/Plano

    Richardson, Texas, 75080

  • Bon Secours Saint Mary's Hospital

    Richmond, Virginia, 23226

  • Virginia Cancer Institute

    Richmond, Virginia, 23229

  • VCU Massey Cancer Center at Stony Point

    Richmond, Virginia, 23235

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Levine Cancer Institute-Rock Hill

    Rock Hill, South Carolina, 29732

  • UW Health Carbone Cancer Center Rockford

    Rockford, Illinois, 61114

  • Sutter Roseville Medical Center

    Roseville, California, 95661

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • Palo Alto Medical Foundation-Santa Cruz

    Santa Cruz, California, 95065

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Vince Lombardi Cancer Clinic-Sheboygan

    Sheboygan, Wisconsin, 53081

  • Atrium Health Cleveland/LCI-Cleveland

    Shelby, North Carolina, 28150

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • Sanford Cancer Center Oncology Clinic

    Sioux Falls, South Dakota, 57104

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • VCU Community Memorial Health Center

    South Hill, Virginia, 23970

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Cleveland Clinic Cancer Center Strongsville

    Strongsville, Ohio, 44136

  • Overlook Hospital

    Summit, New Jersey, 07902

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • Palo Alto Medical Foundation-Sunnyvale

    Sunnyvale, California, 94086

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • SUNY Upstate Medical Center-Community Campus

    Syracuse, New York, 13215

  • Toledo Clinic Cancer Centers-Toledo

    Toledo, Ohio, 43623

  • Munson Medical Center

    Traverse City, Michigan, 49684

  • Upper Valley Medical Center

    Troy, Ohio, 45373

  • Legacy Meridian Park Hospital

    Tualatin, Oregon, 97062

  • Oklahoma Cancer Specialists and Research Institute-Tulsa

    Tulsa, Oklahoma, 74146

  • Vince Lombardi Cancer Clinic-Two Rivers

    Two Rivers, Wisconsin, 54241

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Sutter Solano Medical Center/Cancer Center

    Vallejo, California, 94589

  • Northwest Cancer Center - Valparaiso

    Valparaiso, Indiana, 46383

  • Legacy Cancer Institute Medical Oncology and Day Treatment

    Vancouver, Washington, 98684

  • Legacy Salmon Creek Hospital

    Vancouver, Washington, 98686

  • Upstate Cancer Center at Verona

    Verona, New York, 13478

  • South Pointe Hospital

    Warrensville Heights, Ohio, 44122

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Illinois CancerCare - Washington

    Washington, Illinois, 61571

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

  • ProHealth Waukesha Memorial Hospital

    Waukesha, Wisconsin, 53188

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Aurora Cancer Care-Milwaukee West

    Wauwatosa, Wisconsin, 53226

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • Froedtert West Bend Hospital/Kraemer Cancer Center

    West Bend, Wisconsin, 53095

  • Cleveland Clinic-Weston

    Weston, Florida, 33331

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Shenandoah Oncology PC

    Winchester, Virginia, 22601

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • Cleveland Clinic Wooster Family Health and Surgery Center

    Wooster, Ohio, 44691

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

  • University of Michigan Health - West

    Wyoming, Michigan, 49519

  • Avera Cancer Institute at Yankton

    Yankton, South Dakota, 57078

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

  • Huron Gastroenterology PC

    Ypsilanti, Michigan, 48106

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

Other trials in United States

Canada4 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan, S7N 4H4

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: MAIN-CAV: Phase III Randomized Trial of Maintenance Cabozantinib and Avelumab vs Maintenance Avelumab After First-Line Platinum-Based Chemotherapy in Patients With Metastatic Urothelial Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

  1. 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.

Being tested
Avelumab, Biospecimen Collection, Bone Scan, Cabozantinib S-malate, Computed Tomography
Medical subject headings
Urinary Bladder Neoplasms, Ureteral Neoplasms, Urethral Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called Bavencio, MSB 0010718C, MSB-0010718C, MSB0010718C

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood and urine samples

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Cabozantinib S-malateDrug

    Also called BMS-907351, Cabometyx, Cometriq, XL 184

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT05092958
Study groupRoleWhat they receive
Arm A (avelumab)Active comparatorPatients 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.
Receives: Drug: Avelumab; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm B (avelumab, cabozantinib)ExperimentalPatients 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.
Receives: Drug: Avelumab; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib S-malate; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    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.

    Measured: Time from randomization until death due to any cause, assessed up to 5 years

Secondary outcomes (3)

  1. Progression free survival (PFS)

    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.

    Measured: 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

  2. Tumor response

    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.

    Measured: Up to 5 years

  3. Incidence of adverse events (AE)

    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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2021
  2. Study start3 Jun 2022
  3. Primary completion15 Jul 2029 (estimated)
  4. Study completion15 Jul 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
654 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05092958
Sponsor's protocol ID
NCI-2021-11166
Other IDs
NCI-2021-11166, A032001, A032001, U10CA180821
Status last verified
Jun 2026
First submitted
22 Oct 2021
Last updated
1 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

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