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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05092958
Other study ID # NCI-2021-11166
Secondary ID NCI-2021-11166A0
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date June 3, 2022
Est. completion date December 10, 2024

Study information

Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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). 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.


Description:

PRIMARY OBJECTIVE: I. To evaluate the effect of cabozantinib S-malate (cabozantinib) 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. 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. After completion of study treatment, patients are followed every 30 days through 90 days, then every 3 months for 5 years.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 654
Est. completion date December 10, 2024
Est. primary completion date December 10, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms

  • Advanced Bladder Urothelial Carcinoma
  • Advanced Ureter Urothelial Carcinoma
  • Carcinoma
  • Carcinoma, Transitional Cell
  • Kidney Neoplasms
  • Metastatic Bladder Urothelial Carcinoma
  • Metastatic Renal Pelvis Urothelial Carcinoma
  • Metastatic Ureter Urothelial Carcinoma
  • Metastatic Urethral Urothelial Carcinoma
  • Pelvic Neoplasms
  • Stage III Bladder Cancer AJCC v8
  • Stage III Renal Pelvis and Ureter Cancer AJCC v8
  • Stage III Renal Pelvis Cancer AJCC v8
  • Stage III Ureter Cancer AJCC v8
  • Stage III Urethral Cancer AJCC v8
  • Stage IV Bladder Cancer AJCC v8
  • Stage IV Renal Pelvis and Ureter Cancer AJCC v8
  • Stage IV Renal Pelvis Cancer AJCC v8
  • Stage IV Ureter Cancer AJCC v8
  • Stage IV Urethral Cancer AJCC v8
  • Ureteral Neoplasms
  • Urethral Neoplasms
  • Urinary Bladder Neoplasms

Intervention

Drug:
Avelumab
Given IV
Procedure:
Biospecimen Collection
Undergo collection of blood samples
Bone Scan
Undergo bone scan
Drug:
Cabozantinib S-malate
Given PO
Procedure:
Computed Tomography
Undergo CT
Magnetic Resonance Imaging
Undergo MRI
Other:
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies

Locations

Country Name City State
Canada Cross Cancer Institute Edmonton Alberta
Canada Allan Blair Cancer Centre Regina Saskatchewan
Canada Saskatoon Cancer Centre Saskatoon Saskatchewan
Canada University Health Network-Princess Margaret Hospital Toronto Ontario
United States Avera Cancer Institute-Aberdeen Aberdeen South Dakota
United States Cleveland Clinic Akron General Akron Ohio
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States University Cancer Specialists - Alcoa Alcoa Tennessee
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic - Ames Ames Iowa
United States Trinity Health Saint Joseph Mercy Hospital Ann Arbor Ann Arbor Michigan
United States Sutter Auburn Faith Hospital Auburn California
United States Harold Alfond Center for Cancer Care Augusta Maine
United States Rush - Copley Medical Center Aurora Illinois
United States Advocate Good Shepherd Hospital Barrington Illinois
United States Memorial Sloan Kettering Basking Ridge Basking Ridge New Jersey
United States Bronson Battle Creek Battle Creek Michigan
United States Sanford Joe Lueken Cancer Center Bemidji Minnesota
United States Alta Bates Summit Medical Center-Herrick Campus Berkeley California
United States National Institutes of Health Clinical Center Bethesda Maryland
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Sanford Bismarck Medical Center Bismarck North Dakota
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Prisma Health Cancer Institute - Spartanburg Boiling Springs South Carolina
United States McFarland Clinic - Boone Boone Iowa
United States Trinity Health IHA Medical Group Hematology Oncology - Brighton Brighton Michigan
United States Trinity Health Medical Center - Brighton Brighton Michigan
United States Aurora Cancer Care-Southern Lakes VLCC Burlington Wisconsin
United States Illinois CancerCare-Canton Canton Illinois
United States Trinity Health IHA Medical Group Hematology Oncology - Canton Canton Michigan
United States Trinity Health Medical Center - Canton Canton Michigan
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Illinois CancerCare-Carthage Carthage Illinois
United States Miami Valley Hospital South Centerville Ohio
United States Centralia Oncology Clinic Centralia Illinois
United States Medical University of South Carolina Charleston South Carolina
United States West Virginia University Charleston Division Charleston West Virginia
United States Atrium Health University City/LCI-University Charlotte North Carolina
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Levine Cancer Institute-Ballantyne Charlotte North Carolina
United States Levine Cancer Institute-SouthPark Charlotte North Carolina
United States Chelsea Hospital Chelsea Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital Chelsea Michigan
United States Advocate Illinois Masonic Medical Center Chicago Illinois
United States Northwestern University Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Hematology Oncology Consultants-Clarkston Clarkston Michigan
United States Newland Medical Associates-Clarkston Clarkston Michigan
United States Cleveland Clinic Cancer Center/Fairview Hospital Cleveland Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Southeastern Medical Oncology Center-Clinton Clinton North Carolina
United States MU Health - University Hospital/Ellis Fischel Cancer Center Columbia Missouri
United States Memorial Sloan Kettering Commack Commack New York
United States Atrium Health Cabarrus/LCI-Concord Concord North Carolina
United States New Hampshire Oncology Hematology PA-Concord Concord New Hampshire
United States Siteman Cancer Center at West County Hospital Creve Coeur Missouri
United States Northwest Cancer Center - Main Campus Crown Point Indiana
United States AMG Crystal Lake - Oncology Crystal Lake Illinois
United States UT Southwestern Simmons Cancer Center - RedBird Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Carle at The Riverfront Danville Illinois
United States Dayton Physician LLC - Englewood Dayton Ohio
United States Miami Valley Hospital North Dayton Ohio
United States Premier Blood and Cancer Center Dayton Ohio
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
United States Illinois CancerCare-Dixon Dixon Illinois
United States Advocate Good Samaritan Hospital Downers Grove Illinois
United States Northwest Oncology LLC Dyer Indiana
United States Prisma Health Cancer Institute - Easley Easley South Carolina
United States Marshfield Medical Center-EC Cancer Center Eau Claire Wisconsin
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Advocate Sherman Hospital Elgin Illinois
United States Arnot Ogden Medical Center/Falck Cancer Center Elmira New York
United States Illinois CancerCare-Eureka Eureka Illinois
United States Sanford Broadway Medical Center Fargo North Dakota
United States Sanford Roger Maris Cancer Center Fargo North Dakota
United States Genesee Cancer and Blood Disease Treatment Center Flint Michigan
United States Genesee Hematology Oncology PC Flint Michigan
United States Genesys Hurley Cancer Institute Flint Michigan
United States Hurley Medical Center Flint Michigan
United States McFarland Clinic - Trinity Cancer Center Fort Dodge Iowa
United States UT Southwestern/Simmons Cancer Center-Fort Worth Fort Worth Texas
United States Beebe South Coastal Health Campus Frankford Delaware
United States Atrium Medical Center-Middletown Regional Hospital Franklin Ohio
United States Palo Alto Medical Foundation-Fremont Fremont California
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Northwestern Medicine Cancer Center Delnor Geneva Illinois
United States Aurora Health Care Germantown Health Center Germantown Wisconsin
United States Glens Falls Hospital Glens Falls New York
United States Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina
United States Aurora Cancer Care-Grafton Grafton Wisconsin
United States Corewell Health Grand Rapids Hospitals - Butterworth Hospital Grand Rapids Michigan
United States Trinity Health Grand Rapids Hospital Grand Rapids Michigan
United States Aurora BayCare Medical Center Green Bay Wisconsin
United States Miami Valley Cancer Care and Infusion Greenville Ohio
United States Prisma Health Cancer Institute - Butternut Greenville South Carolina
United States Prisma Health Cancer Institute - Eastside Greenville South Carolina
United States Prisma Health Cancer Institute - Faris Greenville South Carolina
United States Prisma Health Greenville Memorial Hospital Greenville South Carolina
United States Prisma Health Cancer Institute - Greer Greer South Carolina
United States Legacy Mount Hood Medical Center Gresham Oregon
United States Hackensack University Medical Center Hackensack New Jersey
United States Penn State Health Medical Group - Andrews Patel Hematology/Oncology East Harrisburg Pennsylvania
United States Memorial Sloan Kettering Westchester Harrison New York
United States Advocate South Suburban Hospital Hazel Crest Illinois
United States OptumCare Cancer Care at Seven Hills Henderson Nevada
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States Northwest Cancer Center - Hobart Hobart Indiana
United States Saint Mary Medical Center Hobart Indiana
United States Saint Catherine Hospital Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States Mayo Clinic in Florida Jacksonville Florida
United States Southeastern Medical Oncology Center-Jacksonville Jacksonville North Carolina
United States McFarland Clinic - Jefferson Jefferson Iowa
United States Ascension Borgess Cancer Center Kalamazoo Michigan
United States Bronson Methodist Hospital Kalamazoo Michigan
United States West Michigan Cancer Center Kalamazoo Michigan
United States Saint Luke's Hospital of Kansas City Kansas City Missouri
United States Aurora Cancer Care-Kenosha South Kenosha Wisconsin
United States Kettering Medical Center Kettering Ohio
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States University of Tennessee - Knoxville Knoxville Tennessee
United States Northwestern Medicine Lake Forest Hospital Lake Forest Illinois
United States University of Michigan Health - Sparrow Lansing Lansing Michigan
United States Memorial Medical Center - Las Cruces Las Cruces New Mexico
United States OptumCare Cancer Care at Charleston Las Vegas Nevada
United States OptumCare Cancer Care at Fort Apache Las Vegas Nevada
United States Saint Luke's East - Lee's Summit Lee's Summit Missouri
United States AMG Libertyville - Oncology Libertyville Illinois
United States Condell Memorial Hospital Libertyville Illinois
United States Atrium Health Lincoln/LCI-Lincolnton Lincolnton North Carolina
United States Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan
United States Baptist Health Louisville Louisville Kentucky
United States Great Lakes Cancer Management Specialists-Macomb Medical Campus Macomb Michigan
United States Illinois CancerCare-Macomb Macomb Illinois
United States Solinsky Center for Cancer Care Manchester New Hampshire
United States Cleveland Clinic Cancer Center Mansfield Mansfield Ohio
United States Aurora Bay Area Medical Group-Marinette Marinette Wisconsin
United States McFarland Clinic - Marshalltown Marshalltown Iowa
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Hillcrest Hospital Cancer Center Mayfield Heights Ohio
United States Bon Secours Memorial Regional Medical Center Mechanicsville Virginia
United States Froedtert Menomonee Falls Hospital Menomonee Falls Wisconsin
United States Memorial Sloan Kettering Monmouth Middletown New Jersey
United States Bon Secours Saint Francis Medical Center Midlothian Virginia
United States Aurora Cancer Care-Milwaukee Milwaukee Wisconsin
United States Aurora Saint Luke's Medical Center Milwaukee Wisconsin
United States Aurora Sinai Medical Center Milwaukee Wisconsin
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Abbott-Northwestern Hospital Minneapolis Minnesota
United States Hennepin County Medical Center Minneapolis Minnesota
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States Memorial Medical Center Modesto California
United States Memorial Sloan Kettering Bergen Montvale New Jersey
United States Morristown Medical Center Morristown New Jersey
United States Palo Alto Medical Foundation-Camino Division Mountain View California
United States ProHealth D N Greenwald Center Mukwonago Wisconsin
United States The Community Hospital Munster Indiana
United States Women's Diagnostic Center - Munster Munster Indiana
United States Trinity Health Muskegon Hospital Muskegon Michigan
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States Memorial Sloan Kettering Cancer Center New York New York
United States Helen F Graham Cancer Center Newark Delaware
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Cancer and Hematology Centers of Western Michigan - Norton Shores Norton Shores Michigan
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States Drexel Town Square Health Center Oak Creek Wisconsin
United States Advocate Christ Medical Center Oak Lawn Illinois
United States ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin
United States Upstate Cancer Center at Oswego Oswego New York
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Palo Alto Medical Foundation Health Care Palo Alto California
United States Advocate Lutheran General Hospital Park Ridge Illinois
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Illinois CancerCare-Pekin Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Jefferson Methodist Hospital Philadelphia Pennsylvania
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States Mayo Clinic Hospital in Arizona Phoenix Arizona
United States Hope Cancer Center Pontiac Michigan
United States Michigan Healthcare Professionals Pontiac Pontiac Michigan
United States Newland Medical Associates-Pontiac Pontiac Michigan
United States Trinity Health Saint Joseph Mercy Oakland Hospital Pontiac Michigan
United States Legacy Good Samaritan Hospital and Medical Center Portland Oregon
United States Illinois CancerCare-Princeton Princeton Illinois
United States Aurora Cancer Care-Racine Racine Wisconsin
United States Corewell Health Reed City Hospital Reed City Michigan
United States Beebe Health Campus Rehoboth Beach Delaware
United States Valley Medical Center Renton Washington
United States Marshfield Medical Center-Rice Lake Rice Lake Wisconsin
United States UT Southwestern Clinical Center at Richardson/Plano Richardson Texas
United States Bon Secours Saint Mary's Hospital Richmond Virginia
United States VCU Massey Cancer Center at Stony Point Richmond Virginia
United States Virginia Cancer Institute Richmond Virginia
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Mayo Clinic in Rochester Rochester Minnesota
United States Levine Cancer Institute-Rock Hill Rock Hill South Carolina
United States UW Health Carbone Cancer Center Rockford Rockford Illinois
United States Sutter Roseville Medical Center Roseville California
United States Sutter Medical Center Sacramento Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Coborn Cancer Center at Saint Cloud Hospital Saint Cloud Minnesota
United States Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center Saint Joseph Michigan
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Siteman Cancer Center at Christian Hospital Saint Louis Missouri
United States Siteman Cancer Center-South County Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Park Nicollet Clinic - Saint Louis Park Saint Louis Park Minnesota
United States Regions Hospital Saint Paul Minnesota
United States Siteman Cancer Center at Saint Peters Hospital Saint Peters Missouri
United States California Pacific Medical Center-Pacific Campus San Francisco California
United States North Coast Cancer Care Sandusky Ohio
United States Palo Alto Medical Foundation-Santa Cruz Santa Cruz California
United States Prisma Health Cancer Institute - Seneca Seneca South Carolina
United States Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin
United States Atrium Health Cleveland/LCI-Cleveland Shelby North Carolina
United States Memorial Hospital East Shiloh Illinois
United States Avera Cancer Institute Sioux Falls South Dakota
United States Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States VCU Community Memorial Health Center South Hill Virginia
United States Memorial Medical Center Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Marshfield Medical Center-River Region at Stevens Point Stevens Point Wisconsin
United States Stony Brook University Medical Center Stony Brook New York
United States Cleveland Clinic Cancer Center Strongsville Strongsville Ohio
United States Aurora Medical Center in Summit Summit Wisconsin
United States Overlook Hospital Summit New Jersey
United States Palo Alto Medical Foundation-Sunnyvale Sunnyvale California
United States State University of New York Upstate Medical University Syracuse New York
United States SUNY Upstate Medical Center-Community Campus Syracuse New York
United States Toledo Clinic Cancer Centers-Toledo Toledo Ohio
United States Munson Medical Center Traverse City Michigan
United States Upper Valley Medical Center Troy Ohio
United States Legacy Meridian Park Hospital Tualatin Oregon
United States Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma
United States Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin
United States Memorial Sloan Kettering Nassau Uniondale New York
United States Carle Cancer Center Urbana Illinois
United States Sutter Solano Medical Center/Cancer Center Vallejo California
United States Northwest Cancer Center - Valparaiso Valparaiso Indiana
United States Legacy Cancer Institute Medical Oncology and Day Treatment Vancouver Washington
United States Legacy Salmon Creek Hospital Vancouver Washington
United States Upstate Cancer Center at Verona Verona New York
United States South Pointe Hospital Warrensville Heights Ohio
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States Illinois CancerCare - Washington Washington Illinois
United States MedStar Washington Hospital Center Washington District of Columbia
United States ProHealth Waukesha Memorial Hospital Waukesha Wisconsin
United States UW Cancer Center at ProHealth Care Waukesha Wisconsin
United States Aurora Cancer Care-Milwaukee West Wauwatosa Wisconsin
United States Aurora West Allis Medical Center West Allis Wisconsin
United States Froedtert West Bend Hospital/Kraemer Cancer Center West Bend Wisconsin
United States Cleveland Clinic-Weston Weston Florida
United States Marshfield Medical Center - Weston Weston Wisconsin
United States Rice Memorial Hospital Willmar Minnesota
United States Shenandoah Oncology PC Winchester Virginia
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States Cleveland Clinic Wooster Family Health and Surgery Center Wooster Ohio
United States UMass Memorial Medical Center - University Campus Worcester Massachusetts
United States University of Michigan Health - West Wyoming Michigan
United States Avera Cancer Institute at Yankton Yankton South Dakota
United States Rush-Copley Healthcare Center Yorkville Illinois
United States Huron Gastroenterology PC Ypsilanti Michigan
United States Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Ypsilanti Michigan

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Time from randomization until death due to any cause, assessed up to 5 years
Secondary 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. 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
Secondary 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. Up to 5 years
Secondary 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. Up to 5 years
See also
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