NCT04216290|Active Not RecruitingPhase 2FDA Drug

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

Phase II Study of Bladder-SparIng ChemoradiatioN With Durvalumab in Clinical Stage III, Node PosItive BladdeR CancEr (INSPIRE)

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2019-08628EA8185U10CA180820

Study Type

interventional

Target

Locations

1 country

Sites

216

Timeline

RegisteredJan 2020

StartedMar 2021

CompletionMay 2027

Brief Summary

This phase II trial studies the benefit of adding an immunotherapy drug called MEDI4736 (durvalumab) to standard chemotherapy and radiation therapy in treating bladder cancer which has spread to the lymph nodes. Drugs used in standard chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

11mo left

Started Mar 2021

Longer than P75 for phase_2

Geographic Reach

1 country

216 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.2 years study duration

Study Progress85%

Mar 2021May 2027

First Submitted

Initial submission to the registry

December 31, 2019

Completed

2 days until next milestone

First Posted

Study publicly available on registry

January 2, 2020

Completed

1.2 years until next milestone

Study Start

First participant enrolled

March 17, 2021

Completed

4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 4, 2026

Completed

1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 19, 2027

Expected

Last Updated

May 22, 2026

Status Verified

May 1, 2026

Enrollment Period

4.9 years

First QC Date

December 31, 2019

Last Update Submit

May 20, 2026

Conditions

Stage III Bladder Cancer AJCC v8 Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

Clinical complete response (CR)
Defined as CR in bladder and nodes with no distant metastases. This study is designed to detect an improvement in clinical CR rate from 37.5% on the chemoradiation (chemoRT) arm to 62.5% on the chemoRT + durvalumab arm. Patients who receive any chemoRT +/- durvalumab will be included in the interim and final analyses. Those who are unevaluable post chemoRT +/- durvalumab, such as those patients who drop out before completing treatment post randomization or drop out prior to evaluation of first response or those patients who cannot get computed tomography scan and or cystoscopy to evaluate for response will be considered non-responders.
Up to 4 years

Secondary Outcomes (8)

Metastasis-free survival
From randomization to first evidence of metastatic disease or death from any cause, assessed up to 4 years
Bladder-intact event-free survival (BI-EFS)
From randomization to the first BI-EFS event, assessed up to 4 years
Bladder cancer specific survival
From randomization to death from bladder cancer, assessed up to 4 years
Overall survival
From randomization to death from any cause, assessed up to 4 years
Progression-free survival
From randomization to first of local progression, nodal or distant metastasis, or death from any cause, assessed up to 4 years
+3 more secondary outcomes

Study Arms (4)

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

EXPERIMENTAL

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.

Procedure: Biopsy of BladderProcedure: Biospecimen CollectionDrug: CisplatinProcedure: Computed TomographyProcedure: CystoscopyBiological: DurvalumabDrug: FluorouracilDrug: Gemcitabine HydrochlorideProcedure: Magnetic Resonance ImagingDrug: MitomycinRadiation: Radiation Therapy

Step 1, Arm D (radiation therapy, chemotherapy)

ACTIVE COMPARATOR

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.

Procedure: Biopsy of BladderProcedure: Biospecimen CollectionDrug: CisplatinProcedure: Computed TomographyProcedure: CystoscopyDrug: FluorouracilDrug: Gemcitabine HydrochlorideProcedure: Magnetic Resonance ImagingDrug: MitomycinRadiation: Radiation Therapy

Step 2, Arm E (durvalumab)

EXPERIMENTAL

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.

Procedure: Biopsy of BladderProcedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: CystoscopyBiological: DurvalumabProcedure: Magnetic Resonance Imaging

Step 2, Arm F (observation)

ACTIVE COMPARATOR

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.

Procedure: Biopsy of BladderProcedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: CystoscopyProcedure: Magnetic Resonance ImagingOther: Patient Observation

Interventions

Biopsy of BladderPROCEDURE

Undergo bladder biopsy

Also known as: Bladder Biopsy

Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)Step 1, Arm D (radiation therapy, chemotherapy)Step 2, Arm E (durvalumab)Step 2, Arm F (observation)

Biospecimen CollectionPROCEDURE

Undergo tumor tissue and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)Step 1, Arm D (radiation therapy, chemotherapy)Step 2, Arm E (durvalumab)Step 2, Arm F (observation)

CisplatinDRUG

Given IV

Also known as: 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

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

Computed TomographyPROCEDURE

Undergo CT

Also known as: 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

Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)Step 1, Arm D (radiation therapy, chemotherapy)Step 2, Arm E (durvalumab)Step 2, Arm F (observation)

Gemcitabine HydrochlorideDRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

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

Patient ObservationOTHER

Undergo observation

Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

Step 2, Arm F (observation)

CystoscopyPROCEDURE

Undergo cystoscopy

Also known as: CS

Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)Step 1, Arm D (radiation therapy, chemotherapy)Step 2, Arm E (durvalumab)Step 2, Arm F (observation)

DurvalumabBIOLOGICAL

Given IV

Also known as: 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

Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)Step 2, Arm E (durvalumab)

FluorouracilDRUG

Given IV

Also known as: 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

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

Magnetic Resonance ImagingPROCEDURE

Undergo MRI

Also known as: 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

Step 1, Arm C (durvalumab, radiation therapy, chemotherapy)Step 1, Arm D (radiation therapy, chemotherapy)Step 2, Arm E (durvalumab)Step 2, Arm F (observation)

MitomycinDRUG

Given IV

Also known as: 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

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

Radiation TherapyRADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

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

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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:
+21 more criteria

You may not qualify if:

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:
+18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (216)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Alaska Breast Care and Surgery LLC