NCT04164082|Active Not RecruitingPhase 2FDA Drug

Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer

Phase II Trial of Intravesical Gemcitabine and MK-3475 (Pembrolizumab) in the Treatment of Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2019-07573A031803U10CA180821

Study Type

interventional

Target

161

Locations

3 countries

Sites

391

Timeline

RegisteredNov 2019

StartedMar 2020

CompletionDec 2026

Brief Summary

This phase II trial studies the effect of adding pembrolizumab to gemcitabine in treating patients with non-muscle invasive bladder cancer whose cancer does not respond to Bacillus Calmette-Guerin (BCG) treatment. Chemotherapy drugs, such as gemcitabine, 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. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the patient's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding pembrolizumab to gemcitabine may delay the return of BCG-unresponsive bladder cancer for longer period compared to gemcitabine alone.

Trial Health

On Track

Trial Health Score

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

Enrollment

161

participants targeted

Target at P75+ for phase_2

Timeline

8mo left

Started Mar 2020

Longer than P75 for phase_2

Geographic Reach

3 countries

391 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

6.7 years study duration

Study Progress90%

Mar 2020Dec 2026

First Submitted

Initial submission to the registry

November 14, 2019

Completed

1 day until next milestone

First Posted

Study publicly available on registry

November 15, 2019

Completed

4 months until next milestone

Study Start

First participant enrolled

March 18, 2020

Completed

6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 9, 2026

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 9, 2026

Last Updated

April 13, 2026

Status Verified

February 1, 2026

Enrollment Period

6.7 years

First QC Date

November 14, 2019

Last Update Submit

April 9, 2026

Conditions

Stage I Bladder Cancer AJCC v8 Stage 0a Bladder Cancer AJCC v8 Stage 0is Bladder Cancer AJCC v8 Bladder Flat Urothelial Carcinoma In Situ Non-Muscle Invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

Complete response rate in the carcinoma in situ (CIS) subpopulation
A complete response, only for patients with a CIS component, is a cystoscopy without evidence of bladder tumor and negative biopsy (including directed biopsies to any suspicious areas and in addition random bladder biopsies including trigone, left lateral wall, right lateral wall, posterior bladder, dome of bladder, and the prostatic urethra in men), and negative cytology for high grade disease.
At 6 months (end of cycle 8, week 25)
Event-free survival at 18 months
For patients without a documented event and who are still alive, they will be censored at last disease assessment. For patients who start any subsequent ant-cancer therapy without any reported events will be censored at their last disease assessment. will be obtained with a Kaplan-Meier estimator (using the Greenwood formula to estimate the variance) for the entire 153 patient group consisting of patients with CIS, CIS with Ta/T1 or Ta or T1 disease. A 90% confidence interval will be generated for the 18-month EFS estimate.
From the date of study registration to the first documentation of an event or death whichever comes first, assessed up to 18 months

Secondary Outcomes (6)

Incidence of adverse events
Up to 5 years post treatment
Duration of response (DOR)
From the time a patient had a documented response (the time would start at the time a response was first noted) until disease-progression, assessed up to 5 years
Progression-free survival (PFS)
From the date of study registration to the date of progression or death due to any cause, whichever occurs first, assessed up to 5 years
Overall survival (OS)
From the date of study registration to date of death due to any cause, assessed up to 5 years
Cystectomy-free survival
From the date of study registration to the date of cystectomy for all patients
+1 more secondary outcomes

Study Arms (1)

Treatment (pembrolizumab, gemcitabine hydrochloride)

EXPERIMENTAL

INDUCTION: Patients receive pembrolizumab IV over 25-40 minutes on day 1 of cycles 1-4. Patients also receive gemcitabine hydrochloride intravesically on days 1, 8 and 15 of cycles 1 and 2. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning cycle 5, patients with no evidence of disease after induction receive pembrolizumab IV over 25-40 minutes and gemcitabine intravesically on day 1 of each cycle. Treatment repeats every 3 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients with T1 tumors undergo a re-staging TURBT within 60 days of registration. Patients also undergo urine and blood sample collection, bladder biopsy, cystoscopy, CT and MRI throughout the study.

Procedure: Biopsy ProcedureProcedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: CystoscopyDrug: Gemcitabine HydrochlorideProcedure: Magnetic Resonance ImagingBiological: PembrolizumabProcedure: Transurethral Resection of Bladder Tumor