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 (The INSPIRE Study)

STATUS: Active


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.
  • Step 1 (Randomization) Inclusion

  • 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., computed tomography [CT] or magnetic resonance imaging [MRI] or positron emission tomography [PET]/CT) * A lymph node that is < 1 cm on imaging with biopsy confirming involvement with cancer * NOTE: Patients with a negative biopsy of nodes determined to be suspicious on imaging are not eligible. Lymph node biopsy is not mandatory and is per physician discretion. For patients who have non-muscle invasive disease on transurethral resection of bladder tumor (TURBT), the positive nodes must be biopsy-proven or suspicious on PET/CT

  • 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 have 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

  • 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

  • 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 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 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 registration * 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)

  • 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 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

  • 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)

United States
AK
Anchorage
Alaska Breast Care and Surgery LLC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Alaska Oncology and Hematology LLC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Alaska Women's Cancer Care
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Anchorage Associates in Radiation Medicine
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Anchorage Oncology Centre
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Katmai Oncology Group
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

Providence Alaska Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: AKPAMC.OncologyResearchSupport@providence.org

AR
Ft. Smith
Mercy Hospital Fort Smith
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Hot Springs
CHI Saint Vincent Cancer Center Hot Springs
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

CA
Burbank
Providence Saint Joseph Medical Center / Disney Family Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Najee.Boucher@providence.org

Palo Alto
VA Palo Alto Health Care System
Status: ACTIVE
Contact: Site Public Contact

CO
Colorado Springs
Penrose-Saint Francis Healthcare
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Rocky Mountain Cancer Centers-Penrose
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Denver
Porter Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Lakewood
Saint Anthony Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Littleton
Littleton Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Longmont
Longmont United Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Parker
Parker Adventist Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Pueblo
Saint Mary Corwin Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

DE
Frankford
Beebe South Coastal Health Campus
Status: ACTIVE
Contact: Site Public Contact
Email: Dmiskin@Beebehealthcare.org

Newark
Helen F Graham Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: mhayden@christianacare.org

Medical Oncology Hematology Consultants PA
Status: ACTIVE
Contact: Site Public Contact
Email: mhayden@christianacare.org

Rehoboth Beach
Beebe Health Campus
Status: ACTIVE
Contact: Site Public Contact
Email: Dmiskin@Beebehealthcare.org

FL
Fort Lauderdale
Holy Cross Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Miami Beach
Mount Sinai Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: yenrique@msmc.com

IA
Ames
Mary Greeley Medical Center
Status: ACTIVE
Contact: Site Public Contact

McFarland Clinic PC - Ames
Status: ACTIVE
Contact: Site Public Contact
Email: ksoder@mcfarlandclinic.com

Clive
Medical Oncology and Hematology Associates-West Des Moines
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Mercy Cancer Center-West Lakes
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Creston
Greater Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Des Moines
Broadlawns Medical Center
Status: ACTIVE
Contact: Site Public Contact

Iowa Lutheran Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Iowa Methodist Medical Center
Status: ACTIVE
Contact: Site Public Contact

Medical Oncology and Hematology Associates-Des Moines
Status: ACTIVE
Contact: Site Public Contact

Medical Oncology and Hematology Associates-Laurel
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Mercy Medical Center - Des Moines
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

West Des Moines
Mercy Medical Center-West Lakes
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Methodist West Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

ID
Boise
Saint Alphonsus Cancer Care Center-Boise
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Saint Luke's Cancer Institute - Boise
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Caldwell
Saint Alphonsus Cancer Care Center-Caldwell
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Coeur D'Alene
Kootenai Health - Coeur d'Alene
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Fruitland
Saint Luke's Cancer Institute - Fruitland
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Meridian
Idaho Urologic Institute-Meridian
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Saint Luke's Cancer Institute - Meridian
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Nampa
Saint Alphonsus Medical Center-Nampa
Status: ACTIVE
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Saint Luke's Cancer Institute - Nampa
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

Post Falls
Kootenai Clinic Cancer Services - Post Falls
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Twin Falls
Saint Luke's Cancer Institute - Twin Falls
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: eslinget@slhs.org

IL
Aurora
Rush - Copley Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Cancer.Research@rushcopley.com

Bloomington
Illinois CancerCare-Bloomington
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Canton
Illinois CancerCare-Canton
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Carbondale
Memorial Hospital of Carbondale
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: clinical.research@sih.net

Carterville
SIH Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: clinical.research@sih.net

Carthage
Illinois CancerCare-Carthage
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Centralia
Centralia Oncology Clinic
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Chicago
Northwestern University
Status: ACTIVE
Contact: Site Public Contact
Email: cancer@northwestern.edu

Danville
Carle on Vermilion
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

Decatur
Cancer Care Specialists of Illinois - Decatur
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Effingham
Carle Physician Group-Effingham
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

Crossroads Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Eureka
Illinois CancerCare-Eureka
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Galesburg
Illinois CancerCare-Galesburg
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Western Illinois Cancer Treatment Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Hines
Edward Hines Jr VA Hospital
Status: ACTIVE
Contact: Site Public Contact

Kewanee
Illinois CancerCare-Kewanee Clinic
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Macomb
Illinois CancerCare-Macomb
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Mattoon
Carle Physician Group-Mattoon / Charleston
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

Maywood
Loyola University Medical Center
Status: ACTIVE
Contact: Site Public Contact

Mount Vernon
Good Samaritan Regional Health Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

O'Fallon
Cancer Care Center of O'Fallon
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Ottawa
Illinois CancerCare-Ottawa Clinic
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Pekin
Illinois CancerCare-Pekin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Peoria
Illinois CancerCare-Peoria
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Methodist Medical Center of Illinois
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

OSF Saint Francis Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Peru
Illinois CancerCare-Peru
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Valley Radiation Oncology
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Princeton
Illinois CancerCare-Princeton
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Springfield
Memorial Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Springfield Clinic
Status: ACTIVE
Contact: Site Public Contact

Urbana
Carle Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: Research@carle.com

The Carle Foundation Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Research@carle.com

KY
Lexington
Saint Joseph Hospital East
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Saint Joseph Radiation Oncology Resource Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Louisville
Baptist Health Louisville
Status: ACTIVE
Contact: Site Public Contact
Email: Cbcresearch@bhsi.com

Jewish Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

UofL Health Medical Center Northeast
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ctoinfo@louisville.edu

LA
Metairie
East Jefferson General Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: emede1@lsuhsc.edu

LSU Healthcare Network / Metairie Multi-Specialty Clinic
Status: ACTIVE
Contact: Site Public Contact
Email: emede1@lsuhsc.edu

New Orleans
Louisiana State University Health Science Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: emede1@lsuhsc.edu

ME
Bangor
Eastern Maine Medical Center
Status: ACTIVE
Contact: Site Public Contact

Brewer
Lafayette Family Cancer Center-EMMC
Status: ACTIVE
Contact: Site Public Contact

MI
Ann Arbor
Saint Joseph Mercy Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Brighton
Saint Joseph Mercy Brighton
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Brighton
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Canton
Saint Joseph Mercy Canton
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Canton
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Chelsea
Saint Joseph Mercy Chelsea
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Detroit
Ascension Saint John Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: karen.forman@ascension.org

Flint
Genesys Hurley Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: wstrong@ghci.org

Hurley Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: wstrong@ghci.org

Lansing
Sparrow Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Pontiac
21st Century Oncology-Pontiac
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Saint Joseph Mercy Oakland
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Saginaw
Ascension Saint Mary's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: lori.srebinski@ascension.org

Warren
Saint John Macomb-Oakland Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: karen.forman@ascension.org

Ypsilanti
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Status: ACTIVE
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

MN
Brainerd
Essentia Health Saint Joseph's Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Deer River
Essentia Health - Deer River Clinic
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Duluth
Essentia Health Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Essentia Health Saint Mary's Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Miller-Dwan Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Hibbing
Essentia Health Hibbing Clinic
Status: ACTIVE
Contact: Site Public Contact

Sandstone
Essentia Health Sandstone
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Virginia
Essentia Health Virginia Clinic
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

MO
Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Cape Girardeau
Saint Francis Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: sfmc@sfmc.net

Southeast Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Creve Coeur
Siteman Cancer Center at West County Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Farmington
Parkland Health Center - Farmington
Status: ACTIVE
Contact: Site Public Contact

Jefferson City
Capital Region Southwest Campus
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: swooden@mail.crmc.org

Joplin
Mercy Hospital Joplin
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: esmeralda.carrillo@mercy.net

Rolla
Delbert Day Cancer Institute at PCRMC
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: research@phelpshealth.org

Mercy Clinic-Rolla-Cancer and Hematology
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Saint Joseph
Heartland Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: linda.schumacher@mymlc.com

Saint Louis
Mercy Hospital Saint Louis
Status: ACTIVE
Contact: Site Public Contact

Mercy Hospital South
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: janet.lesko@mercy.net

Missouri Baptist Medical Center
Status: ACTIVE
Contact: Site Public Contact

Siteman Cancer Center at Christian Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Siteman Cancer Center-South County
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Washington University School of Medicine
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Sainte Genevieve
Sainte Genevieve County Memorial Hospital
Status: ACTIVE
Contact: Site Public Contact

Springfield
CoxHealth South Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Mercy Hospital Springfield
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Sullivan
Missouri Baptist Sullivan Hospital
Status: ACTIVE
Contact: Site Public Contact

Sunset Hills
Missouri Baptist Outpatient Center-Sunset Hills
Status: ACTIVE
Contact: Site Public Contact

MT
Billings
Billings Clinic Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: research@billingsclinic.org

Bozeman
Bozeman Deaconess Hospital
Status: ACTIVE
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Great Falls
Benefis Healthcare- Sletten Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Great Falls Clinic
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Kalispell
Kalispell Regional Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Missoula
Community Medical Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

NE
Grand Island
CHI Health Saint Francis
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

Kearney
CHI Health Good Samaritan
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Omaha
Alegent Health Bergan Mercy Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Alegent Health Immanuel Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Alegent Health Lakeside Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Creighton University Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

NM
Albuquerque
University of New Mexico Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: LByatt@nmcca.org

OH
Cincinnati
Bethesda North Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Good Samaritan Hospital - Cincinnati
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: Jamesline@osumc.edu

OK
Oklahoma City
Mercy Hospital Oklahoma City
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact

University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

OR
Bend
Saint Charles Health System
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: nosall@stcharleshealthcare.org

Clackamas
Clackamas Radiation Oncology Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Cancer Institute Clackamas Clinic
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Coos Bay
Bay Area Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: cherie.cox@bayareahospital.org

Newberg
Providence Newberg Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Portland
Providence Portland Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

PA
Allentown
Lehigh Valley Hospital-Cedar Crest
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Morgan_M.Horton@lvhn.org

Bethlehem
Lehigh Valley Hospital - Muhlenberg
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Morgan_M.Horton@lvhn.org

Chadds Ford
Christiana Care Health System-Concord Health Center
Status: ACTIVE
Contact: Site Public Contact
Email: mhayden@christianacare.org

East Stroudsburg
Pocono Medical Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: Morgan_M.Horton@lvhn.org

Hershey
Penn State Milton S Hershey Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: CTO@hmc.psu.edu

SC
Gaffney
Gibbs Cancer Center-Gaffney
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: kmertz-rivera@gibbscc.org

Greer
Gibbs Cancer Center-Pelham
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: kmertz-rivera@gibbscc.org

Spartanburg
Spartanburg Medical Center
Status: ACTIVE
Contact: Site Public Contact
Email: kmertz-rivera@gibbscc.org

Union
MGC Hematology Oncology-Union
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: kmertz-rivera@gibbscc.org

TN
Knoxville
University of Tennessee - Knoxville
Status: ACTIVE
Contact: Site Public Contact

TX
Bryan
Saint Joseph Regional Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: ResearchInstituteInquiries@CommonSpirit.org

VA
Martinsville
Sovah Health Martinsville
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Email: sharon.hubbard@lpnt.net

WI
Ashland
Duluth Clinic Ashland
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Northwest Wisconsin Cancer Center
Status: ACTIVE
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Marshfield
Marshfield Medical Center-Marshfield
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Minocqua
Marshfield Clinic-Minocqua Center
Status: ACTIVE
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

WY
Sheridan
Welch Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
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 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 6.5-8 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 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. 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.

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.


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ECOG-ACRIN Cancer Research Group