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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04216290
Other study ID # NCI-2019-08628
Secondary ID NCI-2019-08628EA
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date March 17, 2021
Est. completion date June 30, 2026

Study information

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

Clinical Trial Summary

This phase II trial studies the benefit of adding an immunotherapy drug called MEDI4736 (durvalumab) to standard chemotherapy and radiation therapy in treating bladder cancer which has spread to the lymph nodes. Drugs used in standard chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with durvalumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving chemotherapy and radiation therapy with the addition of durvalumab may work better in helping tumors respond to treatment compared to chemotherapy and radiation therapy alone. Patients with limited regional lymph node involvement may benefit from attempt at bladder preservation, and use of immunotherapy and systemic chemotherapy.


Description:

PRIMARY OBJECTIVE: I. To compare the clinical complete response rate (cCR) after chemoradiotherapy (chemoRT) with or without durvalumab in node-positive bladder cancer patients. SECONDARY OBJECTIVES: I. To compare the toxicity profile in both arms using the Common Terminology Criteria for Adverse Events (CTCAE). II. To estimate the progression-free survival (PFS) in both arms. III. To estimate overall survival (OS) post randomization in both arms. IV. To estimate the bladder intact event free survival (BIEFS) in both arms. V. To estimate the metastasis free survival (MFS) in both arms. VI. To estimate bladder cancer specific survival in both arms. VII. To estimate the complete clinical response duration in both arms. VIII. To estimate salvage cystectomy rates in both arms. EXPLORATORY OBJECTIVE: I. Planned subgroup analyses for clinical outcome (clinical complete response [CR] rate post chemoRT +/- durvalumab, MFS, OS, PFS) based on stratification factors. TRANSLATIONAL OBJECTIVE: I. To collect and bank tumor tissue and blood specimens at pre-and post-treatment with chemoRT +/- durvalumab to determine predictive or prognostic markers. OUTLINE: STEP 1 - Randomization: Patients are randomized to 1 of 2 arms. ARM C: Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes twice a week (BIW) for 6 weeks; cisplatin IV over 30-60 minutes once a week (QW) for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy, cystoscopy, and computed tomography (CT) or magnetic resonance imaging (MRI) on study. Patients may also undergo tumor tissue and blood sample collection on study. ARM D: Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy, cystoscopy, and CT or MRI on study. Patients may also undergo tumor tissue and blood sample collection on study. STEP 2 - Registration: Patients are assigned to 1 of 2 arms. ARM E: Patients previously randomized to Arm C (chemoradiation and durvalumab) who achieve clinical CR or clinical benefit receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy, cystoscopy, and CT or MRI on study. Patients may also undergo tumor tissue and blood sample collection on study. ARM F: Patients previously randomized to Arm D (chemoradiation) who achieve clinical CR or clinical benefit, or patients previously randomized to Arm C with no clinical CR or clinical benefit undergo observation. Patients also undergo bladder biopsy, cystoscopy, and CT or MRI on study. Patients may also undergo tumor tissue and blood sample collection on study. After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 6 months for year 2, and then annually for years 3-4.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 95
Est. completion date June 30, 2026
Est. primary completion date June 30, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Step 1 (Randomization) Inclusion - Patient must be >= 18 years of age - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of step 1 randomization - Patient must have histologically proven pure or mixed urothelial cancer of the bladder - NOTE: Small cell carcinoma is excluded, however other variant histologies are permitted provided a component of urothelial carcinoma is present - Patient must have documented node-positive and non-metastatic disease (any T, any N, M0). Node positivity must have been defined prior to receiving and systemic chemotherapy or induction chemotherapy. Node positivity can fall into either of the following categories and will be defined by imaging and/or biopsy: - A lymph node >= 1.0 cm in short axis on imaging (i.e., CT or MRI or positron emission tomography [PET]/CT) - A lymph node that is < 1 cm on imaging with either a biopsy confirming involvement with cancer - For patients who have received induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, there must be no signs of disease progression (CR/PR or stable disease [SD]) based on restaging imaging and cystoscopy, which consists of: - CT chest, abdomen, and pelvis obtained after completion of induction chemotherapy and within 8 weeks prior to step 1 randomization - NOTE: MRI can be used instead of CT per treating physician discretion - Cystoscopic evaluation and attempt to perform maximal TURBT performed by the participating urologist after completion of induction chemotherapy and within 12 weeks prior to step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file - Patients who achieve CR upon cystoscopy per urologist with no visible tumor (i.e., no need for additional TURBT), are allowed to proceed in the study as adequate resection with no residual disease in bladder - For patients who did not receive induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, the following must be obtained: - CT chest, abdomen, and pelvis completed within 8 weeks prior to step 1 randomization. - NOTE: MRI can be used instead of CT per treating physician discretion - Cystoscopic evaluation and attempt to perform maximal TURBT performed by the participating urologist within 12 weeks prior to Step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file. - For patients who may need repeat TURBT if their old TURBT has fallen out of window: If urologist determine no visible tumor (i.e., no need for additional resection) upon cystoscopy, they are allowed to proceed in the study as complete resection - Patient must agree to undergo CT simulation and treatment planning. If this is the first case registered at the site, then a pre-treatment RT review will be required and will take up to 3 business days. The patient cannot start radiation treatment prior to successful completion of this pre-treatment review. Therefore, careful planning is necessary to meet the deadline of starting radiation within 20 business days of Step 1 randomization - Patients with previous exposure to immune checkpoint inhibitor for non-muscle invasive disease are eligible. If given for NMIBC, the last dose must have been completed > 12 months prior to step 1 randomization - Leukocytes >= 3,000/mcL (obtained < 14 days prior to step 1 randomization) - Absolute neutrophil count (ANC) >= 1,500/mcL (obtained < 14 days prior to step 1 randomization) - Hemoglobin >= 9 g/dL (obtained < 14 days prior to step 1 randomization) - Platelets >= 100,000/mcL (obtained < 14 days prior to step 1 randomization) - Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained < 14 days prior to step 1 randomization) - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained < 14 days prior to step 1 randomization) - Adequate renal function as evidenced by calculated (Cockcroft's formula) creatinine clearance or 24 hours actual creatinine clearance >= 30mL/min. The creatinine used to calculate the clearance result must have been obtained within 14 days prior to step 1 randomization. Actual body weight, not ideal body weight, must be used in the calculation - Patients with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months of step 1 randomization are eligible for this trial - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Site is encouraged to discuss with the study chair if needed prior to enrollment - Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better - Step 2 (Registration: Adjuvant Durvalumab vs. Observation) Inclusion - Patient must have evaluation to determine clinical outcome post step 1 treatment (chemoRT+/- durvalumab) with imaging (CT chest, abdomen, and pelvis)(preferably contrast with urogram, if not contraindicated) and cystoscopy with biopsy confirmation to ensure no progression and absence of >= T2 disease in the bladder. Patient should be registered to step 2 within 28 days from the determination of primary response to step 1 treatment. However, for patients previously on Arm C, an additional 4 week delay to step 2 registration is allowed - Patient on the chemoRT+ durvalumab (Arm C) must meet the following: - Patient must have achieved either complete clinical response OR have demonstrated clinical benefit prior to continuing onto adjuvant durvalumab - Patients who are to go on the adjuvant durvalumab (Arm E) must have recovered to at least grade 2 or less immune related AE prior to starting treatment except for immune related alopecia, clinically asymptomatic endocrinopathies. For patients who may have gotten immune related AEs during chemoRT+ durvalumab (Arm C), step 2 registration could be delayed up to additional 4 weeks to ensure recovery to at least grade 2 or lower prior to starting adjuvant therapy. However patients with durvalumab related AEs that require permanent discontinuation of durvalumab will not continue on the adjuvant treatment regardless of the response - Patient must not have experienced immune related neurological disorder described as Guillain-Barré syndrome, myasthenic syndrome or myasthenia gravis, or meningoencephalitis during chemoRT+ durvalumab treatment - Patient must not have experienced immune related myocarditis or immune related pericarditis during chemoRT+ durvalumab treatment - ANC >= 1,000 mcL (must be obtained < 28 days prior to step 2 registration) - Hemoglobin >= 8g/dL (must be obtained < 28 days prior to step 2 registration) - Platelets >= 70,000 mcL (must be obtained < 28 days prior to step 2 registration) - NOTE: If recovery is not achieved, blood counts could be repeated weekly and step 2 registration could be delayed up to additional 4 weeks - Patient on the chemoRT arm (Arm D) must have achieved either complete clinical response OR have demonstrated clinical benefit prior to be placed on the observation alone arm (Arm F) Exclusion Criteria: - Step 1 (Randomization) Exclusion - Patient must not have received any previous radiation therapy to the pelvic area - Patient must not have presence of concomitant active upper tract tumors or urethra tumors. History of previously adequately treated non-muscle invasive bladder cancer (NMIBC) are eligible; previously treated urothelial cancer or histological variant at any site outside of the urinary bladder are allowed, provided they have been Ta/T1/carcinoma in situ (CIS) and post treatment follow up imaging and endoscopic evaluation shows no evidence of disease - Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to step 1 randomization to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) - Patients must not expect to conceive or father children by using accepted and effected method(s) of contraception or by abstaining from sexual intercourse from the time of Step 1 randomization for the duration of their participation in the study and continue for at least 3 months after the last dose of protocol treatment - For patients with autoimmune conditions, patient must not have history of prior documented autoimmune disease within 2 years prior to step 1 randomization - NOTE: Patient with vitiligo, Grave's disease, eczema or psoriasis (not requiring systemic treatment within 2 years prior to step 1 randomization) are not excluded. Patients with history of completely resolved childhood asthma or atopy are not excluded. Patients with asthma not requiring more than 10 mg/d or equivalent of prednisone are not excluded. Patients with well-controlled hypothyroidism on thyroxine replacement will be eligible as well. Patients with known history of hypoadrenalism on maintenance steroids will be eligible. Patients with type I diabetes mellitus will be eligible, provided their disease is well controlled. History of autoimmune related alopecia is also not an exclusion criteria - Patient with active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) are not eligible - Patient with a history of and/or confirmed pneumonitis are not eligible - Patient with a history of primary immunodeficiency are not eligible - Patient with history of allogeneic organ transplant are not eligible - Patient must not have an active infection, including: - Tuberculosis (based on clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis testing in line with local practice) - Hepatitis B (HBV) (known positive HBV surface antigen [HBsAg] result). Past or resolved HBV infection (defined as the presence of hepatitis b core antibody [anti-HBc] and absence of HBsAg) are eligible - Hepatitis C Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction test is negative for HCV ribonucleic acid (RNA) - Patient must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease) - Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab - NOTE: Patient, if enrolled, must not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab - NOTE: Patient is permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily in order to minimize an overlap of adverse events) - Patient must not have current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: - Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection). - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) - Patient must not have any unresolved toxicity (National Cancer Institute [NCI] CTCAE grade >= 2) from previous anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values - NOTE: Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study chair - NOTE: Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study chair. Documentation of correspondences with the study chair must be kept on file

Study Design


Intervention

Procedure:
Biopsy of Bladder
Undergo bladder biopsy
Biospecimen Collection
Undergo tumor tissue and blood sample collection
Drug:
Cisplatin
Given IV
Procedure:
Computed Tomography
Undergo CT
Cystoscopy
Undergo cystoscopy
Biological:
Durvalumab
Given IV
Drug:
Fluorouracil
Given IV
Gemcitabine Hydrochloride
Given IV
Procedure:
Magnetic Resonance Imaging
Undergo MRI
Drug:
Mitomycin
Given IV
Other:
Patient Observation
Undergo observation
Radiation:
Radiation Therapy
Undergo radiation therapy

Locations

Country Name City State
United States Providence Regional Cancer System-Aberdeen Aberdeen Washington
United States University of New Mexico Cancer Center Albuquerque New Mexico
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 Alaska Breast Care and Surgery LLC Anchorage Alaska
United States Alaska Oncology and Hematology LLC Anchorage Alaska
United States Alaska Women's Cancer Care Anchorage Alaska
United States Anchorage Associates in Radiation Medicine Anchorage Alaska
United States Anchorage Oncology Centre Anchorage Alaska
United States Katmai Oncology Group Anchorage Alaska
United States Providence Alaska Medical Center Anchorage Alaska
United States Trinity Health Saint Joseph Mercy Hospital Ann Arbor Ann Arbor Michigan
United States Duluth Clinic Ashland Ashland Wisconsin
United States Northwest Wisconsin Cancer Center Ashland Wisconsin
United States Emory University Hospital Midtown Atlanta Georgia
United States Emory University Hospital/Winship Cancer Institute Atlanta Georgia
United States Rush - Copley Medical Center Aurora Illinois
United States Saint Louis Cancer and Breast Institute-Ballwin Ballwin Missouri
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States PeaceHealth Saint Joseph Medical Center Bellingham Washington
United States Saint Charles Health System Bend Oregon
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Billings Clinic Cancer Center Billings Montana
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Saint Alphonsus Cancer Care Center-Boise Boise Idaho
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Bozeman Health Deaconess Hospital Bozeman Montana
United States Essentia Health Saint Joseph's Medical Center Brainerd Minnesota
United States Harrison HealthPartners Hematology and Oncology-Bremerton Bremerton Washington
United States Lafayette Family Cancer Center-EMMC Brewer Maine
United States Trinity Health IHA Medical Group Hematology Oncology - Brighton Brighton Michigan
United States Trinity Health Medical Center - Brighton Brighton Michigan
United States Saint Joseph Regional Cancer Center Bryan Texas
United States Providence Saint Joseph Medical Center/Disney Family Cancer Center Burbank California
United States Highline Medical Center-Main Campus Burien Washington
United States Saint Alphonsus Cancer Care Center-Caldwell Caldwell Idaho
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 Southeast Cancer Center Cape Girardeau Missouri
United States Memorial Hospital of Carbondale Carbondale Illinois
United States SIH Cancer Institute Carterville Illinois
United States Illinois CancerCare-Carthage Carthage Illinois
United States Centralia Oncology Clinic Centralia Illinois
United States Providence Regional Cancer System-Centralia Centralia Washington
United States Christiana Care Health System-Concord Health Center Chadds Ford Pennsylvania
United States Chelsea Hospital Chelsea Michigan
United States Northwestern University Chicago Illinois
United States Bethesda North Hospital Cincinnati Ohio
United States Good Samaritan Hospital - Cincinnati Cincinnati Ohio
United States Clackamas Radiation Oncology Center Clackamas Oregon
United States Providence Cancer Institute Clackamas Clinic Clackamas Oregon
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Mission Cancer and Blood - West Des Moines Clive Iowa
United States Kootenai Health - Coeur d'Alene Coeur d'Alene Idaho
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Rocky Mountain Cancer Centers-Penrose Colorado Springs Colorado
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Mercy Hospital Coon Rapids Minnesota
United States Bay Area Hospital Coos Bay Oregon
United States Greater Regional Medical Center Creston Iowa
United States Siteman Cancer Center at West County Hospital Creve Coeur Missouri
United States Carle at The Riverfront Danville Illinois
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Decatur Memorial Hospital Decatur Illinois
United States Essentia Health - Deer River Clinic Deer River Minnesota
United States Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
United States Porter Adventist Hospital Denver Colorado
United States Broadlawns Medical Center Des Moines Iowa
United States Iowa Lutheran Hospital Des Moines Iowa
United States Iowa Methodist Medical Center Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Laurel Des Moines Iowa
United States Ascension Saint John Hospital Detroit Michigan
United States Essentia Health Cancer Center Duluth Minnesota
United States Essentia Health Saint Mary's Medical Center Duluth Minnesota
United States Miller-Dwan Hospital Duluth Minnesota
United States Pocono Medical Center East Stroudsburg Pennsylvania
United States Marshfield Medical Center-EC Cancer Center Eau Claire Wisconsin
United States Swedish Cancer Institute-Edmonds Edmonds Washington
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Illinois CancerCare-Eureka Eureka Illinois
United States Providence Regional Cancer Partnership Everett Washington
United States Parkland Health Center - Farmington Farmington Missouri
United States Genesys Hurley Cancer Institute Flint Michigan
United States Hurley Medical Center Flint Michigan
United States Holy Cross Hospital Fort Lauderdale Florida
United States Mercy Hospital Fort Smith Fort Smith Arkansas
United States Beebe South Coastal Health Campus Frankford Delaware
United States Unity Hospital Fridley Minnesota
United States Saint Luke's Cancer Institute - Fruitland Fruitland Idaho
United States Gibbs Cancer Center-Gaffney Gaffney South Carolina
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Western Illinois Cancer Treatment Center Galesburg Illinois
United States Northwestern Medicine Cancer Center Delnor Geneva Illinois
United States Nebraska Cancer Specialists/Oncology Hematology West PC Grand Island Nebraska
United States Benefis Sletten Cancer Institute Great Falls Montana
United States Great Falls Clinic Great Falls Montana
United States Gibbs Cancer Center-Pelham Greer South Carolina
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States Essentia Health Hibbing Clinic Hibbing Minnesota
United States Edward Hines Jr VA Hospital Hines Illinois
United States CHI Saint Vincent Cancer Center Hot Springs Hot Springs Arkansas
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States Swedish Cancer Institute-Issaquah Issaquah Washington
United States MU Health Care Goldschmidt Cancer Center Jefferson City Missouri
United States Mercy Hospital Joplin Joplin Missouri
United States Kalispell Regional Medical Center Kalispell Montana
United States CHI Health Good Samaritan Kearney Nebraska
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States University of Tennessee - Knoxville Knoxville Tennessee
United States Providence Regional Cancer System-Lacey Lacey Washington
United States Northwestern Medicine Lake Forest Hospital Lake Forest Illinois
United States Saint Anthony Hospital Lakewood Colorado
United States University of Michigan Health - Sparrow Lansing Lansing Michigan
United States Saint Joseph Hospital East Lexington Kentucky
United States Saint Joseph Radiation Oncology Resource Center Lexington Kentucky
United States Littleton Adventist Hospital Littleton Colorado
United States Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan
United States Longmont United Hospital Longmont Colorado
United States PeaceHealth Saint John Medical Center Longview Washington
United States Baptist Health Louisville Louisville Kentucky
United States Jewish Hospital Louisville Kentucky
United States UofL Health Medical Center Northeast Louisville Kentucky
United States Illinois CancerCare-Macomb Macomb Illinois
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Sovah Health Martinsville Martinsville Virginia
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Loyola University Medical Center Maywood Illinois
United States Idaho Urologic Institute-Meridian Meridian Idaho
United States Saint Luke's Cancer Institute - Meridian Meridian Idaho
United States East Jefferson General Hospital Metairie Louisiana
United States LSU Healthcare Network / Metairie Multi-Specialty Clinic Metairie Louisiana
United States Mount Sinai Medical Center Miami Beach Florida
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States Community Medical Center Missoula Montana
United States Good Samaritan Regional Health Center Mount Vernon Illinois
United States Saint Alphonsus Cancer Care Center-Nampa Nampa Idaho
United States Saint Luke's Cancer Institute - Nampa Nampa Idaho
United States Louisiana State University Health Science Center New Orleans Louisiana
United States University Medical Center New Orleans New Orleans Louisiana
United States Helen F Graham Cancer Center Newark Delaware
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Providence Newberg Medical Center Newberg Oregon
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States Mercy Hospital Oklahoma City Oklahoma City Oklahoma
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Alegent Health Bergan Mercy Medical Center Omaha Nebraska
United States Alegent Health Immanuel Medical Center Omaha Nebraska
United States Alegent Health Lakeside Hospital Omaha Nebraska
United States Creighton University Medical Center Omaha Nebraska
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States VA Palo Alto Health Care System Palo Alto California
United States Parker Adventist Hospital Parker Colorado
United States Illinois CancerCare-Pekin Pekin Illinois
United States OSF Saint Francis Radiation Oncology at Pekin Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Methodist Medical Center of Illinois Peoria Illinois
United States OSF Saint Francis Medical Center Peoria Illinois
United States OSF Saint Francis Radiation Oncology at Peoria Cancer Center Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Valley Radiation Oncology Peru Illinois
United States Michigan Healthcare Professionals Pontiac Pontiac Michigan
United States Trinity Health Saint Joseph Mercy Oakland Hospital Pontiac Michigan
United States Providence Portland Medical Center Portland Oregon
United States Providence Saint Vincent Medical Center Portland Oregon
United States Kootenai Clinic Cancer Services - Post Falls Post Falls Idaho
United States Illinois CancerCare-Princeton Princeton Illinois
United States Saint Mary Corwin Medical Center Pueblo Colorado
United States Beebe Health Campus Rehoboth Beach Delaware
United States Marshfield Medical Center-Rice Lake Rice Lake Wisconsin
United States Delbert Day Cancer Institute at PCRMC Rolla Missouri
United States Mercy Clinic-Rolla-Cancer and Hematology Rolla Missouri
United States Ascension Saint Mary's Hospital Saginaw Michigan
United States Heartland Regional Medical Center Saint Joseph Missouri
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Mercy Hospital South Saint Louis Missouri
United States Missouri Baptist Medical Center 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 Siteman Cancer Center at Saint Peters Hospital Saint Peters Missouri
United States Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri
United States Essentia Health Sandstone Sandstone Minnesota
United States Swedish Medical Center-Ballard Campus Seattle Washington
United States Swedish Medical Center-First Hill Seattle Washington
United States PeaceHealth United General Medical Center Sedro-Woolley Washington
United States Welch Cancer Center Sheridan Wyoming
United States Saint Michael Cancer Center Silverdale Washington
United States Spartanburg Medical Center Spartanburg South Carolina
United States CoxHealth South Hospital Springfield Missouri
United States Memorial Medical Center Springfield Illinois
United States Mercy Hospital Springfield Springfield Missouri
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 Missouri Baptist Sullivan Hospital Sullivan Missouri
United States BJC Outpatient Center at Sunset Hills Sunset Hills Missouri
United States Saint Luke's Cancer Institute - Twin Falls Twin Falls Idaho
United States MGC Hematology Oncology-Union Union South Carolina
United States Carle Cancer Center Urbana Illinois
United States The Carle Foundation Hospital Urbana Illinois
United States PeaceHealth Southwest Medical Center Vancouver Washington
United States Essentia Health Virginia Clinic Virginia Minnesota
United States Providence Saint Mary Regional Cancer Center Walla Walla Washington
United States Saint John Macomb-Oakland Hospital Warren Michigan
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States Sibley Memorial Hospital Washington District of Columbia
United States Mercy Medical Center-West Lakes West Des Moines Iowa
United States Methodist West Hospital West Des Moines Iowa
United States Marshfield Medical Center - Weston Weston Wisconsin
United States Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Ypsilanti Michigan

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Clinical complete response (CR) Up to 4 years
Secondary Metastasis-free survival Will be estimated by the Kaplan-Meier method. From randomization to first evidence of metastatic disease or death from any cause, assessed up to 4 years
Secondary Bladder-intact event-free survival (BI-EFS) Will be estimated by the Kaplan-Meier method. From randomization to the first BI-EFS event, assessed up to 4 years
Secondary Bladder cancer specific survival Will be estimated by the Kaplan-Meier method. From randomization to death from bladder cancer, assessed up to 4 years
Secondary Overall survival Will be estimated by the Kaplan-Meier method. From randomization to death from any cause, assessed up to 4 years
Secondary Progression-free survival Will be estimated by the Kaplan-Meier method. From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 4 years
Secondary Complete response duration Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients. From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed up to 4 years
Secondary Salvage cystectomy rate Rate will be reported as a proportion of patients who do not experience clinical benefit after chemoradiotherapy (chemoRT) +/- MEDI4736 (durvalumab) along with a 90% confidence interval. Stratified Cox proportional hazards models will be used to estimate hazard ratios in all eligible patients. Up to 4 years
Secondary Incidence of adverse events Assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Toxicity will be evaluated in all treated patients, regardless of eligibility. Up to 1 year
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