RECRUITING

Study of Pembrolizumab (MK-3475) and Pembrolizumab With Other Investigational Agents in Participants With High Risk Non-muscle Invasive Bladder Cancer (MK-3475-057/KEYNOTE-057)

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

In this study, participants with high risk non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG) therapy and who are considered ineligible for or have refused to undergo radical cystectomy, will receive pembrolizumab therapy or pembrolizumab in combination with other investigational agents. The primary study hypothesis is that treatment with pembrolizumab will result in a clinically meaningful response.

Official Title

A Phase II Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) and Pembrolizumab in Combination With Other Investigational Agents in Subjects With High Risk Non-muscle-Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy

Quick Facts

Study Start:2016-02-10

Study Completion:2030-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02625961

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically-confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta and / or carcinoma in situ \[CIS\]) transitional cell carcinoma of the bladder (mixed histology tumors allowed if transitional cell histology is predominant histology). * Fully resected disease at study entry (residual CIS acceptable) * BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy * Ineligible for radical cystectomy or refusal of radical cystectomy * Available tissue from a newly obtained core biopsy of a tumor lesion not previously irradiated * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Adequate organ function * Female participants of childbearing potential have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception * Male participants must be willing to use an adequate method of contraception	* Centrally assessed muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV) * Centrally assessed concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium * Currently participating or has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks prior to the first dose of study treatment * Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy / Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment * Received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent * Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score ≤7 and prostatic-specific antigen (PSA) undetectable for at least 1 year while off androgen deprivation therapy that was either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation * Active autoimmune disease that has required systemic treatment in the past 2 years * Evidence of interstitial lung disease or active non-infectious pneumonitis * Active infection requiring systemic therapy * Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 120 days after the last dose of study treatment * Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor * Known human immunodeficiency virus (HIV) * Known active Hepatitis B or C infection * Received a live virus vaccine within 30 days of planned start of study treatment * Has had an allogeneic tissue/solid organ transplant

Inclusion Criteria

Exclusion Criteria

* Histologically-confirmed diagnosis of high risk non-muscle-invasive (T1, high grade Ta and / or carcinoma in situ \[CIS\]) transitional cell carcinoma of the bladder (mixed histology tumors allowed if transitional cell histology is predominant histology).
* Fully resected disease at study entry (residual CIS acceptable)
* BCG-unresponsive high risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy
* Ineligible for radical cystectomy or refusal of radical cystectomy
* Available tissue from a newly obtained core biopsy of a tumor lesion not previously irradiated
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Adequate organ function
* Female participants of childbearing potential have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception
* Male participants must be willing to use an adequate method of contraception

* Centrally assessed muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)
* Centrally assessed concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
* Currently participating or has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks prior to the first dose of study treatment
* Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy / Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment
* Received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment or not recovered from adverse events due to a previously administered agent
* Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score ≤7 and prostatic-specific antigen (PSA) undetectable for at least 1 year while off androgen deprivation therapy that was either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation
* Active autoimmune disease that has required systemic treatment in the past 2 years
* Evidence of interstitial lung disease or active non-infectious pneumonitis
* Active infection requiring systemic therapy
* Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial through 120 days after the last dose of study treatment
* Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
* Known human immunodeficiency virus (HIV)
* Known active Hepatitis B or C infection
* Received a live virus vaccine within 30 days of planned start of study treatment
* Has had an allogeneic tissue/solid organ transplant

Contacts and Locations

Study Contact

Toll Free Number

CONTACT

1-888-577-8839

Trialsites@msd.com

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

Call for Information (Investigational Site 0083)

Los Angeles, California, 90095

United States

Call for Information (Investigational Site 0021)

Orange, California, 92868

United States

Call for Information (Investigational Site 0085)

Chicago, Illinois, 60612

United States

Call for Information (Investigational Site 0084)

Indianapolis, Indiana, 46202

United States

Call for Information (Investigational Site 0081)

Wichita, Kansas, 67226

United States

Call for Information (Investigational Site 0023)

Minneapolis, Minnesota, 55455

United States

Call for Information (Investigational Site 0002)

Hackensack, New Jersey, 07601

United States

Call for Information (Investigational Site 0018)

New Brunswick, New Jersey, 08903

United States

Call for Information (Investigational Site 0004)

New York, New York, 10016

United States

Call for Information (Investigational Site 0072)

Cincinnati, Ohio, 45212

United States

Call for Information (Investigational Site 0009)

Cleveland, Ohio, 44106

United States

Call for Information (Investigational Site 0074)

Bala-Cynwyd, Pennsylvania, 19004

United States

Call for Information (Investigational Site 0078)

Myrtle Beach, South Carolina, 29572

United States

Call for Information (Investigational Site 0080)

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2016-02-10

Study Completion Date2030-08-31

Study Record Updates

Study Start Date2016-02-10

Study Completion Date2030-08-31

Terms related to this study

Keywords Provided by Researchers

PD1
PDL1
PD-L1
PD-1

Additional Relevant MeSH Terms

Bladder Cancer