Bladder Cancer
EA8185 / INSPIRE
A Study of Chemotherapy and Radiation Therapy Compared to Chemotherapy and Radiation Therapy plus MEDI4736 (Durvalumab) Immunotherapy for Bladder Cancer Which has Spread to the Lymph Nodes, INSPIRE Trial
STATUS: Closed to Accrual
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 tumor 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.
- STEP 1 (RANDOMIZATION) ELIGIBILITY CRITERIA:
- 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 any 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 or high suspicion of 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/partial response [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 transurethral resection of bladder tumor (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 have 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 not have received any previous radiation therapy to the pelvic area.
- Patient must agree to undergo CT simulation and treatment planning. If this is the first case registered at the site, then a pre-treatment radiation therapy (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.
- 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.
- 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.
- 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.
- 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.
- 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 (known positive hepatitis B virus [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).
- 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.
- 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 coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist (registered trademark) 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.
- STEP 2 (REGISTRACTION: ADJUVANT DURVALUMAB VERSUS [VS] OBSERVATION) ELIGIBILITY CRITERIA:
- 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 adverse event (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).
United States
AK
Anchorage
Alaska Breast Care and Surgery LLC
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Alaska Oncology and Hematology LLC
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Alaska Women's Cancer Care
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Anchorage Associates in Radiation Medicine
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Katmai Oncology Group
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Providence Alaska Medical Center
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AR
Ft. Smith
Mercy Hospital Fort Smith
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Hot Springs
CHI Saint Vincent Cancer Center Hot Springs
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Burbank
Providence Saint Joseph Medical Center/Disney Family Cancer Center
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VA Palo Alto Health Care System
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CO
Colorado Springs
Penrose-Saint Francis Healthcare
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Porter Adventist Hospital
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Saint Anthony Hospital
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Littleton Adventist Hospital
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Longmont United Hospital
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Parker Adventist Hospital
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Washington
Sibley Memorial Hospital
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Millville
Beebe South Coastal Health Campus
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Newark
Helen F Graham Cancer Center
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Medical Oncology Hematology Consultants PA
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Rehoboth Beach
Beebe Health Campus
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Fort Lauderdale
Holy Cross Hospital
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Miami Beach
Mount Sinai Medical Center
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GA
Atlanta
Emory University Hospital Midtown
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Emory University Hospital/Winship Cancer Institute
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Ames
Mary Greeley Medical Center
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McFarland Clinic - Ames
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Clive
Mercy Cancer Center-West Lakes
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Mission Cancer and Blood - West Des Moines
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Creston
Greater Regional Medical Center
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Des Moines
Broadlawns Medical Center
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Iowa Lutheran Hospital
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Iowa Methodist Medical Center
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Mercy Medical Center - Des Moines
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Mission Cancer and Blood - Laurel
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Iowa City
University of Iowa/Holden Comprehensive Cancer Center
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West Des Moines
Mercy Medical Center-West Lakes
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Methodist West Hospital
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ID
Boise
Saint Alphonsus Cancer Care Center-Boise
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Saint Luke's Cancer Institute - Boise
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Caldwell
Saint Alphonsus Cancer Care Center-Caldwell
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Coeur D'Alene
Kootenai Health - Coeur d'Alene
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Fruitland
Saint Luke's Cancer Institute - Fruitland
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Meridian
Idaho Urologic Institute-Meridian
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Saint Luke's Cancer Institute - Meridian
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Nampa
Saint Alphonsus Cancer Care Center-Nampa
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Saint Luke's Cancer Institute - Nampa
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Post Falls
Kootenai Clinic Cancer Services - Post Falls
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Twin Falls
Saint Luke's Cancer Institute - Twin Falls
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IL
Aurora
Rush - Copley Medical Center
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Bloomington
Illinois CancerCare-Bloomington
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Canton
Illinois CancerCare-Canton
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Carbondale
Memorial Hospital of Carbondale
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Carterville
SIH Cancer Institute
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Carthage
Illinois CancerCare-Carthage
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Centralia
Centralia Oncology Clinic
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Chicago
Northwestern University
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Danville
Carle at The Riverfront
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DeKalb
Northwestern Medicine Cancer Center Kishwaukee
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Decatur
Cancer Care Specialists of Illinois - Decatur
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Decatur Memorial Hospital
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Effingham
Carle Physician Group-Effingham
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Crossroads Cancer Center
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Eureka
Illinois CancerCare-Eureka
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Galesburg
Illinois CancerCare-Galesburg
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Western Illinois Cancer Treatment Center
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Geneva
Northwestern Medicine Cancer Center Delnor
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Hines
Edward Hines Jr VA Hospital
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Kewanee
Illinois CancerCare-Kewanee Clinic
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Lake Forest
Northwestern Medicine Lake Forest Hospital
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Macomb
Illinois CancerCare-Macomb
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Mattoon
Carle Physician Group-Mattoon/Charleston
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Maywood
Loyola University Medical Center
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Mount Vernon
Good Samaritan Regional Health Center
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O'Fallon
Cancer Care Center of O'Fallon
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Ottawa
Illinois CancerCare-Ottawa Clinic
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Pekin
Illinois CancerCare-Pekin
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OSF Saint Francis Radiation Oncology at Pekin
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Peoria
Illinois CancerCare-Peoria
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Methodist Medical Center of Illinois
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Peru
Illinois CancerCare-Peru
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Valley Radiation Oncology
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Princeton
Illinois CancerCare-Princeton
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Springfield
Memorial Medical Center
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Southern Illinois University School of Medicine
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Springfield Clinic
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Urbana
Carle Cancer Center
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Warrenville
Northwestern Medicine Cancer Center Warrenville
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KY
Lexington
Saint Joseph Hospital East
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Louisville
Baptist Health Louisville
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Jewish Hospital
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LA
Metairie
East Jefferson General Hospital
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New Orleans
Louisiana State University Health Science Center
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MA
Boston
Massachusetts General Hospital Cancer Center
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MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
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ME
Bangor
Eastern Maine Medical Center
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Brewer
Lafayette Family Cancer Center-EMMC
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MI
Ann Arbor
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Brighton
Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Trinity Health Medical Center - Brighton
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Canton
Trinity Health IHA Medical Group Hematology Oncology - Canton
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Trinity Health Medical Center - Canton
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Chelsea
Chelsea Hospital
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Detroit
Henry Ford Health Saint John Hospital
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Flint
Genesys Hurley Cancer Institute
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Hurley Medical Center
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Lansing
University of Michigan Health - Sparrow Lansing
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Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
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Pontiac
Michigan Healthcare Professionals Pontiac
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Saginaw
MyMichigan Medical Center Saginaw
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Warren
Saint John Macomb-Oakland Hospital
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Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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MN
Brainerd
Essentia Health Saint Joseph's Medical Center
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Coon Rapids
Mercy Hospital
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Deer River
Essentia Health - Deer River Clinic
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Email: CancerTrials@EssentiaHealth.org
Duluth
Essentia Health Cancer Center
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Email: CancerTrials@EssentiaHealth.org
Essentia Health Saint Mary's Medical Center
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Miller-Dwan Hospital
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Fridley
Unity Hospital
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Hibbing
Essentia Health Hibbing Clinic
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Sandstone
Essentia Health Sandstone
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Virginia
Essentia Health Virginia Clinic
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MO
Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
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Cape Girardeau
Saint Francis Medical Center
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Email: sfmc@sfmc.net
Southeast Cancer Center
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Creve Coeur
Siteman Cancer Center at West County Hospital
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Email: info@siteman.wustl.edu
Farmington
Parkland Health Center - Farmington
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Jefferson City
MU Health Care Goldschmidt Cancer Center
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Email: swooden@mail.crmc.org
Joplin
Mercy Hospital Joplin
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Email: esmeralda.carrillo@mercy.net
Rolla
Delbert Day Cancer Institute at PCRMC
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Email: research@phelpshealth.org
Mercy Clinic-Rolla-Cancer and Hematology
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Saint Joseph
Heartland Regional Medical Center
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Email: linda.schumacher@mymlc.com
Saint Louis
Mercy Hospital Saint Louis
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Mercy Hospital South
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Missouri Baptist Medical Center
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Siteman Cancer Center at Christian Hospital
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Email: info@siteman.wustl.edu
Siteman Cancer Center-South County
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Email: info@siteman.wustl.edu
Washington University School of Medicine
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Email: info@siteman.wustl.edu
Saint Peters
Siteman Cancer Center at Saint Peters Hospital
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Email: info@siteman.wustl.edu
Sainte Genevieve
Sainte Genevieve County Memorial Hospital
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Springfield
CoxHealth South Hospital
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Mercy Hospital Springfield
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Sullivan
Missouri Baptist Sullivan Hospital
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Sunset Hills
BJC Outpatient Center at Sunset Hills
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MT
Billings
Billings Clinic Cancer Center
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Email: research@billingsclinic.org
Bozeman
Bozeman Health Deaconess Hospital
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Email: mccinfo@mtcancer.org
Great Falls
Benefis Sletten Cancer Institute
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Email: mccinfo@mtcancer.org
Great Falls Clinic
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Kalispell
Kalispell Regional Medical Center
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Missoula
Community Medical Center
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NE
Grand Island
Nebraska Cancer Specialists/Oncology Hematology West PC
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Kearney
CHI Health Good Samaritan
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Email: ResearchInstituteInquiries@CommonSpirit.org
Omaha
Alegent Health Bergan Mercy Medical Center
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Email: ResearchInstituteInquiries@CommonSpirit.org
Alegent Health Immanuel Medical Center
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Alegent Health Lakeside Hospital
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Creighton University Medical Center
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NM
Albuquerque
University of New Mexico Cancer Center
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Email: HSC-ClinicalTrialInfo@salud.unm.edu
OH
Cincinnati
Bethesda North Hospital
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Email: ResearchInstituteInquiries@CommonSpirit.org
Good Samaritan Hospital - Cincinnati
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Email: ResearchInstituteInquiries@CommonSpirit.org
Columbus
Ohio State University Comprehensive Cancer Center
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Email: Jamesline@osumc.edu
OK
Oklahoma City
Mercy Hospital Oklahoma City
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University of Oklahoma Health Sciences Center
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Email: ou-clinical-trials@ouhsc.edu
OR
Bend
Saint Charles Health System
Contact: Site Public Contact
Email: nosall@stcharleshealthcare.org
Clackamas
Clackamas Radiation Oncology Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org
Providence Cancer Institute Clackamas Clinic
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org
Coos Bay
Bay Area Hospital
Contact: Site Public Contact
Email: cherie.cox@bayareahospital.org
Newberg
Providence Newberg Medical Center
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Email: CanRsrchStudies@providence.org
Portland
Providence Portland Medical Center
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Email: CanRsrchStudies@providence.org
Providence Saint Vincent Medical Center
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Email: CanRsrchStudies@providence.org
PA
Allentown
Lehigh Valley Hospital-Cedar Crest
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Email: Morgan_M.Horton@lvhn.org
Bethlehem
Lehigh Valley Hospital - Muhlenberg
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Email: Morgan_M.Horton@lvhn.org
Chadds Ford
Christiana Care Health System-Concord Health Center
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Email: lbarone@christianacare.org
East Stroudsburg
Pocono Medical Center
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Email: Morgan_M.Horton@lvhn.org
Hershey
Penn State Milton S Hershey Medical Center
Contact: Site Public Contact
Email: CTO@hmc.psu.edu
SC
Gaffney
Gibbs Cancer Center-Gaffney
Contact: Site Public Contact
Email: kmertz-rivera@gibbscc.org
Greer
Gibbs Cancer Center-Pelham
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Email: kmertz-rivera@gibbscc.org
Spartanburg
Spartanburg Medical Center
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Email: kmertz-rivera@gibbscc.org
Union
MGC Hematology Oncology-Union
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Email: kmertz-rivera@gibbscc.org
TN
Knoxville
University of Tennessee - Knoxville
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TX
Bryan
Saint Joseph Regional Cancer Center
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Email: ResearchInstituteInquiries@CommonSpirit.org
VA
Martinsville
Sovah Health Martinsville
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Email: sharon.hubbard@lpnt.net
WA
Aberdeen
Providence Regional Cancer System-Aberdeen
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Email: deidre.dillon@providence.org
Bellingham
PeaceHealth Saint Joseph Medical Center
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Bremerton
Harrison HealthPartners Hematology and Oncology-Bremerton
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Email: clinicaltrials@sfmc-gi.org
Burien
Highline Medical Center-Main Campus
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Email: ResearchInstituteInquiries@CommonSpirit.org
Centralia
Providence Regional Cancer System-Centralia
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Email: deidre.dillon@providence.org
Edmonds
Swedish Cancer Institute-Edmonds
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Email: PCRC-NCORP@Swedish.org
Everett
Providence Regional Cancer Partnership
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Email: marilyn.birchman@providence.org
Issaquah
Swedish Cancer Institute-Issaquah
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Email: PCRC-NCORP@Swedish.org
Lacey
Providence Regional Cancer System-Lacey
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Email: deidre.dillon@providence.org
Longview
PeaceHealth Saint John Medical Center
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Email: kmakin-bond@peacehealth.org
Seattle
Swedish Medical Center-Ballard Campus
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Email: PCRC-NCORP@Swedish.org
Swedish Medical Center-First Hill
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Email: PCRC-NCORP@Swedish.org
Sedro-Woolley
PeaceHealth United General Medical Center
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Email: lkey@peacehealth.org
Silverdale
Saint Michael Cancer Center
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Vancouver
PeaceHealth Southwest Medical Center
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Email: kmakin-bond@peacehealth.org
Walla Walla
Providence Saint Mary Regional Cancer Center
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Email: Cheryl.Dodd@providence.org
WI
Ashland
Duluth Clinic Ashland
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Email: CancerTrials@EssentiaHealth.org
Northwest Wisconsin Cancer Center
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Email: CancerTrials@EssentiaHealth.org
Eau Claire
Marshfield Medical Center-EC Cancer Center
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Email: oncology.clinical.trials@marshfieldresearch.org
Marshfield
Marshfield Medical Center-Marshfield
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Email: oncology.clinical.trials@marshfieldresearch.org
Minocqua
Marshfield Clinic-Minocqua Center
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Email: oncology.clinical.trials@marshfieldresearch.org
Rice Lake
Marshfield Medical Center-Rice Lake
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Email: oncology.clinical.trials@marshfieldresearch.org
Stevens Point
Marshfield Medical Center-River Region at Stevens Point
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Email: oncology.clinical.trials@marshfieldresearch.org
Weston
Marshfield Medical Center - Weston
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org
WY
Sheridan
Welch Cancer Center
Contact: Site Public Contact
Email: mccinfo@mtcancer.org
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; or 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 on study, cystoscopy on study and during follow-up, as well as computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. 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; or 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 on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. 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 on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. 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 undergo observation. Patients also undergo bladder biopsy on study, cystoscopy on study and during follow-up, as well as CT or MRI throughout the trial. 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.
Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.
The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.