Pembrolizumab (MK3475), Gemcitabine, and Concurrent Hypofractionated Radiation Therapy for Muscle-Invasive Urothelial Cancer of the Bladder
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02621151|
Recruitment Status : Active, not recruiting
First Posted : December 3, 2015
Last Update Posted : January 7, 2021
|Condition or disease||Intervention/treatment||Phase|
|Muscle-invasive Urothelial Cancer of the Bladder||Biological: Pembrolizumab Procedure: Transurethral Resection of Bladder Tumor Drug: Gemcitabine Radiation: External Beam Radiation Therapy||Phase 2|
The investigators hypothesize that the addition of immune checkpoint inhibition with pembrolizumab, an anti-PD-1 inhibitor, to chemo-radiation therapy to the bladder may work to both increase eradication of local tumor as well as distant micrometastases through heightened immune surveillance.
Due to the lack of a previous phase I trial establishing the safety of this combination (pembrolizumab, gemcitabine, and radiation therapy (RT)), an initial safety lead-in cohort of 3 to 6 patients is enrolled for assessing dose-limiting toxicities. Similar to the Phase I 3+3 design, if there is no or only one patient in that cohort experiencing a dose-limiting toxicity, the trial continues to the Phase II part to enroll additional 48 patients for efficacy evaluation.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of MK3475 in Combination With Gemcitabine and Concurrent Hypofractionated Radiation Therapy as Bladder Sparing Treatment for Muscle-Invasive Urothelial Cancer of the Bladder|
|Actual Study Start Date :||August 11, 2016|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||December 2025|
Experimental: Pembrolizumab, Gemcitabine, and RT
Procedure: Transurethral Resection of Bladder Tumor
Other Name: Gemzar
Radiation: External Beam Radiation Therapy
- Two-year bladder-intact disease-free survival rate [ Time Frame: 2 years ]Bladder-intact disease-free survival is defined as time from initiation of protocol therapy until the development of muscle-invasive bladder cancer recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death, or cystectomy.
- Safety (adverse events) of the protocol therapy [ Time Frame: From beginning of protocol therapy to 90 days after the end of radiation therapy ]The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) 4.
- Complete response (CR) rate [ Time Frame: up to 21 weeks ]The CR rate is the percentage of patients who have achieved CR. At the completion of protocol therapy, patients undergo standard cystoscopy, exam under anesthesia and transurethral resection of bladder tumor to document pathologic response. CR requires no tumor palpable on bimanual examination under anesthesia, no tumor visible on cystoscopy, negative tumor site biopsy, and negative urine cytology.
- Overall survival [ Time Frame: up to 5 years ]Defined as time to death from beginning of protocol therapy.
- Metastasis-free survival [ Time Frame: up to 5 years ]Defined as time to the development of radiographic distant metastases from beginning of protocol therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02621151
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Michigan|
|University of Michigan Health System|
|Ann Arbor, Michigan, United States, 48109|
|United States, New York|
|NYU Perlmutter Cancer Center|
|New York, New York, United States, 10016|
|Memorial Sloan Kettering|
|New York, New York, United States, 10065|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599-7305|
|Principal Investigator:||Arjun Balar, MD||NYU Perlmutter Cancer Center|