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

NCT ID: NCT04216290

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-17

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Bladder Urothelial Carcinoma Stage III Bladder Cancer AJCC v8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)

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 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 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.

Group Type EXPERIMENTAL

Biopsy of Bladder

Intervention Type PROCEDURE

Undergo bladder biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo tumor tissue and blood sample collection

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cystoscopy

Intervention Type PROCEDURE

Undergo cystoscopy

Durvalumab

Intervention Type BIOLOGICAL

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Mitomycin

Intervention Type DRUG

Given IV

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Step 1, Arm D (radiation therapy, chemotherapy)

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.

Group Type ACTIVE_COMPARATOR

Biopsy of Bladder

Intervention Type PROCEDURE

Undergo bladder biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo tumor tissue and blood sample collection

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cystoscopy

Intervention Type PROCEDURE

Undergo cystoscopy

Fluorouracil

Intervention Type DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Mitomycin

Intervention Type DRUG

Given IV

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Step 2, Arm E (durvalumab)

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.

Group Type EXPERIMENTAL

Biopsy of Bladder

Intervention Type PROCEDURE

Undergo bladder biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo tumor tissue and blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cystoscopy

Intervention Type PROCEDURE

Undergo cystoscopy

Durvalumab

Intervention Type BIOLOGICAL

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Step 2, Arm F (observation)

Patients previously randomized to Arm D (chemoradiation) who achieve clinical CR or clinical benefit undergo observation 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.

Group Type ACTIVE_COMPARATOR

Biopsy of Bladder

Intervention Type PROCEDURE

Undergo bladder biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo tumor tissue and blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cystoscopy

Intervention Type PROCEDURE

Undergo cystoscopy

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Patient Observation

Intervention Type OTHER

Undergo observation

Interventions

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Biopsy of Bladder

Undergo bladder biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo tumor tissue and blood sample collection

Intervention Type PROCEDURE

Cisplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Cystoscopy

Undergo cystoscopy

Intervention Type PROCEDURE

Durvalumab

Given IV

Intervention Type BIOLOGICAL

Fluorouracil

Given IV

Intervention Type DRUG

Gemcitabine Hydrochloride

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Mitomycin

Given IV

Intervention Type DRUG

Patient Observation

Undergo observation

Intervention Type OTHER

Radiation Therapy

Undergo radiation therapy

Intervention Type RADIATION

Other Intervention Names

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Bladder Biopsy Biological Sample Collection Biospecimen Collected Specimen Collection Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography CS Imfinzi Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer MEDI 4736 MEDI-4736 MEDI4736 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 dFdCyd Difluorodeoxycytidine Hydrochloride Gemcitabine HCI Gemzar LY 188011 LY-188011 LY188011 Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Ametycine Jelmyto MITO Mito-C Mito-Medac Mitocin Mitocin-C Mitolem Mitomycin C Mitomycin pyelocalyceal Mitomycin-C Mitomycin-X Mitomycine C Mitosol Mitozytrex Mutamycin Mutamycine NCI-C04706 Active Surveillance deferred therapy expectant management Observation Watchful Waiting Cancer Radiotherapy Energy Type ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation

Eligibility Criteria

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Inclusion Criteria

* 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.

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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Monika Joshi

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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Anchorage Associates in Radiation Medicine

Anchorage, Alaska, United States

Site Status

Alaska Breast Care and Surgery LLC

Anchorage, Alaska, United States

Site Status

Alaska Oncology and Hematology LLC

Anchorage, Alaska, United States

Site Status

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Site Status

Anchorage Oncology Centre

Anchorage, Alaska, United States

Site Status

Katmai Oncology Group

Anchorage, Alaska, United States

Site Status

Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

Mercy Hospital Fort Smith

Fort Smith, Arkansas, United States

Site Status

CHI Saint Vincent Cancer Center Hot Springs

Hot Springs, Arkansas, United States

Site Status

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Site Status

VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

Site Status

AdventHealth Porter

Denver, Colorado, United States

Site Status

Saint Anthony Hospital

Lakewood, Colorado, United States

Site Status

AdventHealth Littleton

Littleton, Colorado, United States

Site Status

Longmont United Hospital

Longmont, Colorado, United States

Site Status

AdventHealth Parker

Parker, Colorado, United States

Site Status

Saint Mary Corwin Medical Center

Pueblo, Colorado, United States

Site Status

Beebe South Coastal Health Campus

Millville, Delaware, United States

Site Status

Helen F Graham Cancer Center

Newark, Delaware, United States

Site Status

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Site Status

Beebe Health Campus

Rehoboth Beach, Delaware, United States

Site Status

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho, United States

Site Status

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, United States

Site Status

Idaho Urologic Institute-Meridian

Meridian, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, United States

Site Status

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, United States

Site Status

Rush-Copley Medical Center

Aurora, Illinois, United States

Site Status

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status

Memorial Hospital of Carbondale

Carbondale, Illinois, United States

Site Status

SIH Cancer Institute

Carterville, Illinois, United States

Site Status

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status

Centralia Oncology Clinic

Centralia, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Carle at The Riverfront

Danville, Illinois, United States

Site Status

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States

Site Status

Carle Physician Group-Effingham

Effingham, Illinois, United States

Site Status

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Site Status

Western Illinois Cancer Treatment Center

Galesburg, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Site Status

Edward Hines Jr VA Hospital

Hines, Illinois, United States

Site Status

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

Site Status

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

SSM Health Good Samaritan

Mount Vernon, Illinois, United States

Site Status

Cancer Care Center of O'Fallon

O'Fallon, Illinois, United States

Site Status

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Site Status

OSF Saint Francis Radiation Oncology at Pekin

Pekin, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Peoria, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peru

Peru, Illinois, United States

Site Status

Valley Radiation Oncology

Peru, Illinois, United States

Site Status

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Springfield Clinic

Springfield, Illinois, United States

Site Status

Springfield Memorial Hospital

Springfield, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

The Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status

Mary Greeley Medical Center

Ames, Iowa, United States

Site Status

McFarland Clinic - Ames

Ames, Iowa, United States

Site Status

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, United States

Site Status

Greater Regional Medical Center

Creston, Iowa, United States

Site Status

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, United States

Site Status

Broadlawns Medical Center

Des Moines, Iowa, United States

Site Status

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, United States

Site Status

Iowa Lutheran Hospital

Des Moines, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Methodist West Hospital

West Des Moines, Iowa, United States

Site Status

Mercy Medical Center-West Lakes

West Des Moines, Iowa, United States

Site Status

Saint Joseph Radiation Oncology Resource Center

Lexington, Kentucky, United States

Site Status

Saint Joseph Hospital East

Lexington, Kentucky, United States

Site Status

Jewish Hospital

Louisville, Kentucky, United States

Site Status

Baptist Health Louisville

Louisville, Kentucky, United States

Site Status

UofL Health Medical Center Northeast

Louisville, Kentucky, United States

Site Status

East Jefferson General Hospital

Metairie, Louisiana, United States

Site Status

LSU Healthcare Network / Metairie Multi-Specialty Clinic

Metairie, Louisiana, United States

Site Status

Louisiana State University Health Science Center

New Orleans, Louisiana, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Lafayette Family Cancer Center-EMMC

Brewer, Maine, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, United States

Site Status

Trinity Health Medical Center - Brighton

Brighton, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, United States

Site Status

Trinity Health Medical Center - Canton

Canton, Michigan, United States

Site Status

Chelsea Hospital

Chelsea, Michigan, United States

Site Status

Henry Ford Health Saint John Hospital

Detroit, Michigan, United States

Site Status

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

University of Michigan Health - Sparrow Lansing

Lansing, Michigan, United States

Site Status

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, United States

Site Status

Michigan Healthcare Professionals Pontiac

Pontiac, Michigan, United States

Site Status

Trinity Health Saint Joseph Mercy Oakland Hospital

Pontiac, Michigan, United States

Site Status

MyMichigan Medical Center Saginaw

Saginaw, Michigan, United States

Site Status

Henry Ford Health Warren Hospital

Warren, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, United States

Site Status

Essentia Health Saint Joseph's Medical Center

Brainerd, Minnesota, United States

Site Status

Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Essentia Health - Deer River Clinic

Deer River, Minnesota, United States

Site Status

Essentia Health Cancer Center

Duluth, Minnesota, United States

Site Status

Essentia Health Saint Mary's Medical Center

Duluth, Minnesota, United States

Site Status

Miller-Dwan Hospital

Duluth, Minnesota, United States

Site Status

Unity Hospital

Fridley, Minnesota, United States

Site Status

Essentia Health Hibbing Clinic

Hibbing, Minnesota, United States

Site Status

Essentia Health Sandstone

Sandstone, Minnesota, United States

Site Status

Essentia Health Virginia Clinic

Virginia, Minnesota, United States

Site Status

Mercy Oncology and Hematology - Clayton-Clarkson

Ballwin, Missouri, United States

Site Status

Mercy Cancer Center - Cape Girardeau

Cape Girardeau, Missouri, United States

Site Status

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status

Parkland Health Center - Farmington

Farmington, Missouri, United States

Site Status

MU Health Care Goldschmidt Cancer Center

Jefferson City, Missouri, United States

Site Status

Mercy Hospital Joplin

Joplin, Missouri, United States

Site Status

Mercy Clinic-Rolla-Cancer and Hematology

Rolla, Missouri, United States

Site Status

Phelps Health Delbert Day Cancer Institute

Rolla, Missouri, United States

Site Status

Heartland Regional Medical Center

Saint Joseph, Missouri, United States

Site Status

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, Missouri, United States

Site Status

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status

CoxHealth South Hospital

Springfield, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital South

St Louis, Missouri, United States

Site Status

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

Missouri Baptist Sullivan Hospital

Sullivan, Missouri, United States

Site Status

BJC Outpatient Center at Sunset Hills

Sunset Hills, Missouri, United States

Site Status

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Bozeman Health Deaconess Hospital

Bozeman, Montana, United States

Site Status

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status

Great Falls Clinic

Great Falls, Montana, United States

Site Status

Logan Health Medical Center

Kalispell, Montana, United States

Site Status

Community Medical Center

Missoula, Montana, United States

Site Status

Nebraska Cancer Specialists/Oncology Hematology West PC

Grand Island, Nebraska, United States

Site Status

CHI Health Good Samaritan

Kearney, Nebraska, United States

Site Status

Alegent Health Immanuel Medical Center

Omaha, Nebraska, United States

Site Status

Alegent Health Bergan Mercy Medical Center

Omaha, Nebraska, United States

Site Status

Alegent Health Lakeside Hospital

Omaha, Nebraska, United States

Site Status

Creighton University Medical Center

Omaha, Nebraska, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Good Samaritan Hospital - Cincinnati

Cincinnati, Ohio, United States

Site Status

Bethesda North Hospital

Cincinnati, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Mercy Hospital Oklahoma City

Oklahoma City, Oklahoma, United States

Site Status

Saint Charles Health System

Bend, Oregon, United States

Site Status

Clackamas Radiation Oncology Center

Clackamas, Oregon, United States

Site Status

Providence Cancer Institute Clackamas Clinic

Clackamas, Oregon, United States

Site Status

Bay Area Hospital

Coos Bay, Oregon, United States

Site Status

Providence Newberg Medical Center

Newberg, Oregon, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Providence Saint Vincent Medical Center

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania, United States

Site Status

Pocono Medical Center

East Stroudsburg, Pennsylvania, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Gibbs Cancer Center-Gaffney

Gaffney, South Carolina, United States

Site Status

Gibbs Cancer Center-Pelham

Greer, South Carolina, United States

Site Status

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Site Status

SMC Center for Hematology Oncology Union

Union, South Carolina, United States

Site Status

University of Tennessee - Knoxville

Knoxville, Tennessee, United States

Site Status

Saint Joseph Regional Cancer Center

Bryan, Texas, United States

Site Status

Sovah Health Martinsville

Martinsville, Virginia, United States

Site Status

Providence Regional Cancer System-Aberdeen

Aberdeen, Washington, United States

Site Status

PeaceHealth Saint Joseph Medical Center

Bellingham, Washington, United States

Site Status

Highline Medical Center-Main Campus

Burien, Washington, United States

Site Status

Providence Regional Cancer System-Centralia

Centralia, Washington, United States

Site Status

Swedish Cancer Institute-Edmonds

Edmonds, Washington, United States

Site Status

Providence Regional Cancer Partnership

Everett, Washington, United States

Site Status

Swedish Cancer Institute-Issaquah

Issaquah, Washington, United States

Site Status

Providence Regional Cancer System-Lacey

Lacey, Washington, United States

Site Status

PeaceHealth Saint John Medical Center

Longview, Washington, United States

Site Status

Swedish Medical Center-Ballard Campus

Seattle, Washington, United States

Site Status

Swedish Medical Center-First Hill

Seattle, Washington, United States

Site Status

PeaceHealth United General Medical Center

Sedro-Woolley, Washington, United States

Site Status

Saint Michael Cancer Center

Silverdale, Washington, United States

Site Status

PeaceHealth Southwest Medical Center

Vancouver, Washington, United States

Site Status

Providence Saint Mary Regional Cancer Center

Walla Walla, Washington, United States

Site Status

Duluth Clinic Ashland

Ashland, Wisconsin, United States

Site Status

Northwest Wisconsin Cancer Center

Ashland, Wisconsin, United States

Site Status

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, United States

Site Status

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Site Status

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, United States

Site Status

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, United States

Site Status

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, United States

Site Status

Marshfield Medical Center - Weston

Weston, Wisconsin, United States

Site Status

Welch Cancer Center

Sheridan, Wyoming, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2019-08628

Identifier Type: REGISTRY

Identifier Source: secondary_id

EA8185

Identifier Type: OTHER

Identifier Source: secondary_id

EA8185

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2019-08628

Identifier Type: -

Identifier Source: org_study_id