Status and phase
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About
This is an open-label, window of opportunity platform study for subjects with muscle-invasive bladder cancer (MIBC) who are deemed ineligible or refuse cisplatin-based neoadjuvant chemotherapy and are scheduled to undergo definitive surgery (radical cystectomy), or are planning to undergo trimodality therapy (maximal transurethral resection of the bladder tumor followed by concurrent chemoradiation).
The primary objective of this study is to assess changes to immunogenomic markers after treatment with pembrolizumab alone and in combination with the selective class I histone deacetylase (HDAC) inhibitor (entinostat).
Full description
The study will enroll 20 subjects with a confirmed diagnosis of MIBC (cT2-T4aN0M0) who are planned for definitive therapy with either radical cystectomy without cisplatin-based neoadjuvant chemotherapy or trimodality therapy. Subjects who are planned to undergo radical cystectomy must be deemed ineligible for (based on consensus criteria) [1] or refuse neoadjuvant cisplatin-based chemotherapy. Prior to study entry, subjects must consent to having tissue collected for research purposes during the scheduled cystectomy or maximal TURBT. After screening and enrollment, baseline blood and archived transurethral resection of the bladder tumor (TURBT) tumor tissue will be collected from each subject for baseline analyses. Subjects will then start on clinical trial treatment followed by either radical cystectomy or maximal TURBT followed by chemoradiation.
Blood and tumor will be collected from each subject at the time of cystectomy or maximal TURBT. The investigators do not anticipate delays in surgery due to the planned schedule of the preoperative treatment administration for the purposes of this study and based on the phase II ENCORE 601 trial (pembrolizumab and entinostat in melanoma) which reported an acceptable safety profile. Phase I data identified grade 1/2 fatigue as the most common entinostat-related toxicity, with neutropenia and anemia only occurring at doses exceeding those proposed for this study. Safety stopping rules for drug-related toxicity will dictate whether the trial should be halted if subjects are experiencing drug-related toxicity that delays or interferes with standard of care procedures.
Enrollment
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Inclusion criteria
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
-Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in the protocol, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
20 participants in 2 patient groups
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Central trial contact
Julie Maccarone; Shamina Williams
Data sourced from clinicaltrials.gov
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