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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, the INSPIRE Study

Trial Status: Active

This phase II trial studies how well chemotherapy and radiation therapy alone works compared to chemotherapy and radiation therapy plus MEDI4736 (durvalumab) immunotherapy 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. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with durvalumab may induce changes in body’s immune system 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.

Inclusion Criteria

  • Step 1 (Registration) Inclusion
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of registration
  • 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
  • Prior to receiving any induction chemotherapy, patient must have documented node-positive and non-metastatic disease (any T, N1-2 M0). For non-muscle invasive disease on transurethral resection of bladder tumor (TURBT), node positive disease MUST be biopsy proven for patient to be eligible * Node positivity will be defined by the official interpretation of imaging studies. Positive lymph nodes must be imaging read with suspicious lymph node (LN) >= 1.0 cm in short axis to be eligible, with or without biopsy as documented by a radiologist at the treating center. LN Biopsy is not mandatory but encouraged if feasible and safe per physician discretion. Patients with a negative biopsy of nodes determined to be suspicious on imaging are not eligible * Patients with clinical N3 disease are ineligible
  • Induction Chemotherapy Requirements * For patients registered to this protocol post-completion of induction systemic chemotherapy: ** Patient must have received at least 3 cycles of induction chemotherapy (cisplatin-based chemotherapy OR non-cisplatin based chemotherapy) with no evidence of progressive disease (PD) on post-chemotherapy imaging. The last dose of chemotherapy must be within 12 weeks of registration ** Patient who have received more than 3 cycles of induction systemic chemotherapy are also eligible ** Patient must have had a CR, PR or SD to induction chemotherapy on standard imaging *** NOTE: Patients who have only received 2 cycles of induction chemotherapy and demonstrated clinical response (complete response [CR] OR partial response [PR], OR stable disease [SD]) may be considered for enrollment only after consultation and approval by the study chair under exceptional circumstances where 3rd cycle cannot be delivered. Documentation of correspondences with the study chair must be kept on file. We encourage all patients to get 3 cycles of induction chemotherapy * For patients registered to this protocol prior to starting induction systemic chemotherapy: ** Patient must agree to a planned treatment with 3 cycles of induction chemotherapy (physician's choice) ** Patient will again be restaged after completion of induction chemotherapy and prior to randomization to chemoRT +/- MEDI4736 (durvalumab) ** Patient must have a CR, PR or SD to induction chemotherapy on standard imaging prior to randomization to chemoradiotherapy
  • History of previously adequately treated non-muscle invasive bladder cancer (NMIBC) are not excluded; presence of concomitant active upper tract tumors or urethra tumors are not allowed. 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
  • Previous exposure to immune checkpoint inhibitor for non-muscle invasive disease is allowed. If given for NMIBC, the last dose must have been completed > 12 months prior to registration
  • For female patients registered on the study * Women 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 female of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy * A female of childbearing potential is defined as any woman, 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)
  • For patients registered prior to induction chemotherapy only: * Women of childbearing potential and sexually active males 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 registration 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 registration)
  • Absolute neutrophil count >= 1,500/mcL (obtained < 14 days prior to registration)
  • Hemoglobin >= 9 g/dL (obtained < 14 days prior to registration)
  • Platelets >= 100,000/mcL (obtained < 14 days prior to registration)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained < 14 days prior to registration)
  • 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 registration)
  • Must have 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 registration. 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 registration 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 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 2B or better
  • Patient must have a life expectancy of at least 12 weeks, as determined by the treating physician
  • Patient must be willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations, including follow-up
  • Step 2 (Randomization) Inclusion Criteria
  • Patient must have an ECOG performance status of 0-1 at the time of randomization
  • Patient must undergo selection of concurrent chemotherapy regimen
  • Patient must agree to undergo CT simulation and treatment planning on the day of randomization. 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 with approximately 3 weeks of randomization and within 12 weeks of the end of induction chemotherapy. We anticipate that the radiation oncologist should get at least 3 weeks of time between CT simulation and start of chemoRT
  • Chemoradiotherapy should be planned to start up to 12 weeks after the end of induction chemotherapy, but after imaging and cystoscopic restaging, randomization, and any pretreatment radiation quality assurance (QA) that is required
  • Women 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 females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy * A female of childbearing potential is defined as any woman, 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)
  • Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse at least one week prior to the start of treatment and continue for at least 3 months after the last dose of the protocol treatment
  • Leukocytes >= 3,000/mcL (obtained < 14 days prior to randomization)
  • Absolute neutrophil count >= 1,500/mcL (obtained < 14 days prior to randomization)
  • Hemoglobin >= 9 g/dL (obtained < 14 days prior to randomization)
  • Platelets >= 100,000/mcL (obtained < 14 days prior to randomization)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained < 14 days prior to randomization)
  • AST (SGOT)/ALT (SGPT) =< 2.5 x institutional ULN (obtained < 14 days prior to randomization)
  • Must have adequate renal function as evidenced by calculated (Cockcroft’s formula) creatinine clearance or 24 hours actual creatinine clearance >= 30 mL/min. The creatinine used to calculate the clearance result must have been obtained within 14 days prior to randomization. Actual body weight, not ideal body weight, must be used in the calculation
  • Step 3 (Post chemoRT+/- MEDI4736 [durvalumab], prior to starting adjuvant MEDI4736 [durvalumab] versus [vs.] observation) Inclusion Criteria
  • Patient must have evaluation to determine clinical outcome post chemoRT+/- MEDI4736 (durvalumab) with imaging and cystoscopy with biopsy confirmation to ensure no progression and absence of >= T2 disease in the bladder
  • Patient must have achieved either complete clinical response OR have demonstrated clinical benefit prior to continuing onto adjuvant MEDI4736 (durvalumab)
  • Patients who are to go on the adjuvant MEDI4736 (durvalumab) arm must have recovered to at least grade 2 or less immune related adverse events (AE) prior to starting treatment except for immune related alopecia, clinically asymptomatic endocrinopathies. For patients who may have gotten immune related AEs during chemoRT+ MEDI4736 (durvalumab), 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 MEDI4736 (durvalumab) related AEs that require permanent discontinuation of MEDI4736 (durvalumab) will not continue on the adjuvant treatment regardless of the response
  • ANC >= 1,000 mcL (within 4 weeks of start of day 1 [D1] of adjuvant treatment)
  • Hemoglobin >= 8 g/dL (within 4 weeks of start of D1 of adjuvant treatment)
  • Platelets >= 70,000 mcL (within 4 weeks of start of D1 of adjuvant treatment)
  • Patient on the chemoRT arm must have achieved either complete clinical response OR have demonstrated clinical benefit prior to be placed on the observation alone arm

Exclusion Criteria

  • Step 1 (Registration) Exclusion
  • Patient must not have received any previous radiation therapy to the pelvic area
  • Autoimmune conditions: patient must not have history of prior documented autoimmune disease within the past 2 years * NOTE: Patient with vitiligo, Grave’s disease, eczema or psoriasis (not requiring systemic treatment within the past 2 years) 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) will be excluded * Patient with a history of and/or confirmed pneumonitis will not be eligible * Patient with a history of primary immunodeficiency will not be eligible * Patient with history of allogeneic organ transplant are not eligible
  • 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 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 * Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study chair * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with MEDI4736 (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 (Randomization) Exclusion Criteria
  • Patient must have no signs of progression (CR/PR or SD) based on restaging imaging and cystoscopy after completion of induction chemotherapy, which consists of: * Computed tomography (CT) chest, abdomen, or pelvis. Magnetic resonance imaging (MRI) pelvis can be used instead of CT per treating physician discretion. The imaging must be done within 4 weeks prior to randomization * Cystoscopic evaluation and attempt to perform maximal transurethral resection of bladder tumor (TURBT) performed by the participating urologist ideally within 8 weeks but up to 10 weeks is allowed prior to 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 of file
  • Autoimmune conditions: Patient must not have a history of active or prior documented autoimmune disease within the past 2 years * NOTE: Patient with vitiligo, Grave’s disease, eczema or psoriasis (not requiring systemic treatment within the past 2 years) are not excluded. Patients with history of completely resolved childhood asthma or atopy are not excluded. Patients with asthma not requiring more than 10mg/d or equivalent of prednisone are not excluded. Patient 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 (DM) 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) will be excluded * Patient with a history of and/or confirmed pneumonitis will be excluded * Patient with a history of primary immunodeficiency will be excluded * Patient with history of allogeneic organ transplant are excluded
  • 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 cannot have received live attenuated vaccine within 30 days prior to the fist dose of MEDI4736 (durvalumab) * NOTE: Patients, if enrolled, should not receive live vaccine whilst receiving MEDI4736 (durvalumab) and up to 30 days after the last dose of MEDI4736 (durvalumab)
  • Patient must not have current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 (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)
  • Step 3 (Post chemoRT+/- MEDI4736 [durvalumab], prior to starting adjuvant MEDI4736 [durvalumab] vs. observation) Exclusion Criteria
  • Patient must not have experienced immune related neurological disorder described as Guillain-Barre syndrome, myasthenic syndrome or myasthenia gravis, or meningoencephalitis during chemoRT+ MEDI4736 (durvalumab) treatment
  • Patient must not have experienced immune related myocarditis or immune related pericarditis during chemoRT+ MEDI4736 (durvalumab) treatment

Arkansas

Ft. Smith
Mercy Hospital Fort Smith
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-378-9373
Hot Springs
CHI Saint Vincent Cancer Center Hot Springs
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Colorado

Colorado Springs
Penrose-Saint Francis Healthcare
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Rocky Mountain Cancer Centers-Penrose
Status: ACTIVE
Contact: Site Public Contact
Phone: 303-777-2663
Denver
Porter Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Lakewood
Saint Anthony Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Littleton
Littleton Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Longmont
Longmont United Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Parker
Parker Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Pueblo
Saint Mary Corwin Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Florida

Fort Lauderdale
Holy Cross Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 954-267-7750

Idaho

Boise
Saint Alphonsus Cancer Care Center-Boise
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Caldwell
Saint Alphonsus Cancer Care Center-Caldwell
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Coeur D'Alene
Kootenai Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060
Meridian
Idaho Urologic Institute-Meridian
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Nampa
Saint Alphonsus Medical Center-Nampa
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Post Falls
Kootenai Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060

Illinois

Aurora
Rush - Copley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 630-978-6212
Bloomington
Illinois CancerCare-Bloomington
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Canton
Illinois CancerCare-Canton
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Carbondale
Memorial Hospital of Carbondale
Status: ACTIVE
Contact: Site Public Contact
Phone: 618-457-5200
Carterville
SIH Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 618-985-3333
Carthage
Illinois CancerCare-Carthage
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Centralia
Centralia Oncology Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-876-4740
Danville
Carle on Vermilion
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
Decatur
Cancer Care Specialists of Illinois - Decatur
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-876-4740
Decatur Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-876-4740
Effingham
Carle Physician Group-Effingham
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
Crossroads Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-876-4740
Eureka
Illinois CancerCare-Eureka
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Galesburg
Illinois CancerCare-Galesburg
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Western Illinois Cancer Treatment Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-344-2831
Kewanee
Illinois CancerCare-Kewanee Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Macomb
Illinois CancerCare-Macomb
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Mattoon
Carle Physician Group-Mattoon / Charleston
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 708-226-4357
Mount Vernon
Good Samaritan Regional Health Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 618-242-4600
O'Fallon
Cancer Care Center of O'Fallon
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-876-4762
Ottawa
Illinois CancerCare-Ottawa Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Pekin
Illinois CancerCare-Pekin
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Peoria
Illinois CancerCare-Peoria
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Methodist Medical Center of Illinois
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
OSF Saint Francis Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Peru
Illinois CancerCare-Peru
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Valley Radiation Oncology
Status: ACTIVE
Contact: Site Public Contact
Phone: 815-664-4141
Princeton
Illinois CancerCare-Princeton
Status: ACTIVE
Contact: Site Public Contact
Phone: 309-243-3605
Springfield
Memorial Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-788-3528
Southern Illinois University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Phone: 217-545-7929
Springfield Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-444-7541
Urbana
Carle Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532
The Carle Foundation Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-446-5532

Iowa

Ames
Mary Greeley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-956-4132
McFarland Clinic PC - Ames
Status: ACTIVE
Contact: Site Public Contact
Phone: 515-239-4734
Clive
Medical Oncology and Hematology Associates-West Des Moines
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Mercy Cancer Center-West Lakes
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Creston
Greater Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Des Moines
Medical Oncology and Hematology Associates-Laurel
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Mercy Medical Center - Des Moines
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
West Des Moines
Mercy Medical Center-West Lakes
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Kentucky

Lexington
Saint Joseph Hospital East
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Saint Joseph Radiation Oncology Resource Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Louisville
Jewish Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Jewish Hospital Medical Center Northeast
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Louisiana

Metairie
East Jefferson General Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 504-210-3539
LSU Healthcare Network / Metairie Multi-Specialty Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 504-210-3539
New Orleans
Louisiana State University Health Science Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 504-210-3539

Michigan

Ann Arbor
Saint Joseph Mercy Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Brighton
Saint Joseph Mercy Brighton
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Canton
Saint Joseph Mercy Canton
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Chelsea
Saint Joseph Mercy Chelsea
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Detroit
Ascension Saint John Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Flint
Genesys Hurley Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Hurley Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Lansing
Sparrow Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Livonia
Saint Mary Mercy Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Pontiac
21st Century Oncology-Pontiac
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Saint Joseph Mercy Oakland
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Saginaw
Ascension Saint Mary's Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Warren
Saint John Macomb-Oakland Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671

Missouri

Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-251-7058
Cape Girardeau
Saint Francis Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-334-2230
Email: sfmc@sfmc.net
Southeast Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-651-5550
Farmington
Parkland Health Center - Farmington
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-996-5569
Jefferson City
Capital Region Southwest Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-632-4814
Joplin
Mercy Hospital Joplin
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-556-3074
Rolla
Delbert Day Cancer Institute at PCRMC
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-458-8776
Mercy Clinic-Rolla-Cancer and Hematology
Status: ACTIVE
Contact: Site Public Contact
Phone: 573-458-6379
Saint Joseph
Heartland Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 816-271-7937
Saint Louis
Mercy Hospital Saint Louis
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-251-7066
Mercy Hospital South
Status: ACTIVE
Contact: Site Public Contact
Missouri Baptist Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-996-5569
Sainte Genevieve
Sainte Genevieve County Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-996-5569
Springfield
CoxHealth South Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-269-4520
Mercy Hospital Springfield
Status: ACTIVE
Contact: Site Public Contact
Phone: 417-269-4520
Sullivan
Missouri Baptist Sullivan Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-996-5569
Sunset Hills
Missouri Baptist Outpatient Center-Sunset Hills
Status: ACTIVE
Contact: Site Public Contact
Phone: 314-996-5569

Montana

Billings
Billings Clinic Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 800-996-2663
Bozeman
Bozeman Deaconess Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060
Great Falls
Benefis Healthcare- Sletten Cancer Institute
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060
Great Falls Clinic
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060
Kalispell
Kalispell Regional Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060
Missoula
Community Medical Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060

Nebraska

Grand Island
CHI Health Saint Francis
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Kearney
CHI Health Good Samaritan
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Omaha
Alegent Health Bergan Mercy Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Alegent Health Immanuel Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Alegent Health Lakeside Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Creighton University Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Ohio

Cincinnati
Bethesda North Hospital
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Good Samaritan Hospital - Cincinnati
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Oklahoma

Oklahoma City
Mercy Hospital Oklahoma City
Status: ACTIVE
Contact: Site Public Contact
Phone: 405-752-3402

Pennsylvania

Allentown
Lehigh Valley Hospital-Cedar Crest
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
Bethlehem
Lehigh Valley Hospital - Muhlenberg
Status: ACTIVE
Contact: Site Public Contact
Phone: 734-712-3671
East Stroudsburg
Pocono Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 570-422-1700
Hershey
Penn State Milton S Hershey Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 717-531-3779

Texas

Bryan
Saint Joseph Regional Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Washington

Bremerton
Harrison HealthPartners Hematology and Oncology-Bremerton
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Harrison Medical Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518
Burien
Highline Medical Center-Main Campus
Status: ACTIVE
Contact: Site Public Contact
Phone: 308-398-6518

Wyoming

Sheridan
Welch Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Phone: 406-969-6060

PRIMARY OBJECTIVE:

I. To compare the clinical complete response rate (cCR) after chemoradiotherapy (chemoRT) with or without MEDI4736 (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+/- MEDI4736 [durvalumab], MFS, OS, PFS) based on stratification factors.

TRANSLATIONAL OBJECTIVE:

I. To collect specimens- urine, blood, stool and tissue, at pre- and post-treatment, at 6 months and 12 months’ time from completing chemoRT+/- MEDI4736 (durvalumab) to determine predictive or prognostic markers.

OUTLINE:

STEP 1 - REGISTRATION: Patients are assigned to 1 of 2 arms.

ARM A: Patients registered after completion of >= 3 cycles of induction chemotherapy proceed to Step 2 - Randomization.

ARM B: Chemotherapy naive patients receive 1 of 4 chemotherapy regimens: gemcitabine hydrochloride intravenously (IV) over 30-60 minutes on days 1 and 8 every 21 days for 3 cycles; carboplatin IV over 30-60 minutes and gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 every 21 days for 3 cycles; gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and cisplatin IV 30-60 minutes on day 1 every 21 days for 3 cycles; or methotrexate IV over 3 minutes, vinblastine sulfate IV over 3 minutes, doxorubicin hydrochloride IV over 5 minutes, and cisplatin IV over 30-60 minutes on day 1 every 14 days for 3 cycles. Cycles repeat in the absence of disease progression or unacceptable toxicity.

STEP 2 - RANDOMIZATION: Patients are randomized to 1 of 2 arms.

ARM C: Patients undergo radiation therapy for 6-8 weeks. Beginning 4 days before or after starting radiation therapy, patients receive durvalumab IV over 60 minutes on day 1. Cycles repeat every 21 days for 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 weekly for 6 weeks; cisplatin IV over 30-60 minutes for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity.

ARM D: Patients undergo radiation therapy for 6-8 weeks. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes twice weekly for 6 weeks; cisplatin IV over 30-60 minutes for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity.

STEP 3 - REGISTRATION (POST CONCURRENT CHEMORT +/- DURVALUMAB): 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. Cycles repeat every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

ARM F: Patients previously randomized to Arm D who achieve clinical CR or clinical benefit, or patients previously randomized to Arm C with no clinical CR or clinical benefit undergo observation.

After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 6 months for 1 year, and then annually for 1 year.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
ECOG-ACRIN Cancer Research Group

Principal Investigator
Monika Joshi

  • Primary ID EA8185
  • Secondary IDs NCI-2019-08628
  • Clinicaltrials.gov ID NCT04216290