NCT03775265|Active Not RecruitingPhase 3FDA Drug

Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer

Phase III Randomized Trial of Concurrent Chemoradiotherapy With or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2018-03264S1806U10CA180888

Study Type

interventional

Target

475

Locations

1 country

Sites

366

Timeline

RegisteredDec 2018

StartedJun 2019

CompletionJun 2027

Brief Summary

This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.

Trial Health

On Track

Trial Health Score

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

Enrollment

475

participants targeted

Target at P50-P75 for phase_3

Timeline

13mo left

Started Jun 2019

Longer than P75 for phase_3

Geographic Reach

1 country

366 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

8 years study duration

Study Progress87%

Jun 2019Jun 2027

First Submitted

Initial submission to the registry

December 12, 2018

Completed

1 day until next milestone

First Posted

Study publicly available on registry

December 13, 2018

Completed

6 months until next milestone

Study Start

First participant enrolled

June 3, 2019

Completed

8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2027

Last Updated

May 4, 2026

Status Verified

February 1, 2026

Enrollment Period

8 years

First QC Date

December 12, 2018

Last Update Submit

May 1, 2026

Conditions

Bladder Urothelial Carcinoma Stage II Bladder Cancer AJCC v8 Stage IIIA Bladder Cancer AJCC v8 Muscle Invasive Bladder Carcinoma

Outcome Measures

Primary Outcomes (1)

Bladder intact event-free survival (BI-EFS)
At each time point, futility will be evaluated, and in the latter two analyses, efficacy will also be evaluated as specified. The final BI-EFS intent-to-treat analysis will be conducted using a stratified logrank test stratifying on stratification factors, and testing treatment at the one-sided significance level of 0.022 to account for multiple interim testing. The hazard ratio (HR) will be estimated using a stratified Cox proportional hazards model and the 95% confidence interval (CI) for the HR will be provided. Results from an unstratified analysis will also be provided. Kaplan-Meier methodology will be used to estimate the median BI-EFS for each treatment arm.
From the date of randomization to the first documentation of a BI-EFS event, assessed up to 5 years

Secondary Outcomes (8)

Overall survival (OS)
From date of randomization to death from any cause, assessed up to 5 years
Modified bladder intact event-free survival (mBI-EFS)
From date of randomization to the first documentation of a mBI-EFS event, assessed within 90 days
Biopsy response
At 18 weeks
Complete response duration
From the date of the biopsy documenting the complete response to the time of muscle invasive recurrence, local progression, evidence of metastatic disease or death due to any cause, assessed at 18 weeks
Progression-free survival
From date of randomization to first radiologic or histologic evidence of local progression, nodal or distant metastasis, or death due to any cause, assessed up to 5 years
+3 more secondary outcomes

Other Outcomes (1)

Treatment interactions
Up to 5 years

Study Arms (2)

Arm I (RT, chemotherapy)

ACTIVE COMPARATOR

Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks concurrent with RT, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

Procedure: Biopsy of BladderDrug: CisplatinProcedure: Computed TomographyProcedure: CystoscopyDrug: FluorouracilDrug: GemcitabineProcedure: Magnetic Resonance ImagingDrug: MitomycinOther: Quality-of-Life AssessmentRadiation: Radiation TherapyOther: Survey AdministrationProcedure: Transurethral Resection of Bladder Tumor

Arm II (RT, chemotherapy, atezolizumab)

EXPERIMENTAL

Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.

Drug: AtezolizumabProcedure: Biopsy of BladderDrug: CisplatinProcedure: Computed TomographyProcedure: CystoscopyDrug: FluorouracilDrug: GemcitabineProcedure: Magnetic Resonance ImagingDrug: MitomycinOther: Quality-of-Life AssessmentRadiation: Radiation TherapyOther: Survey AdministrationProcedure: Transurethral Resection of Bladder Tumor

Interventions

AtezolizumabDRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Arm II (RT, chemotherapy, atezolizumab)

Biopsy of BladderPROCEDURE

Undergo a bladder biopsy

Also known as: Bladder Biopsy