Study of Mocetinostat in Patients With Urothelial Carcinoma Having Inactivating Alterations of Specific Genes

Study Overview
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Brief Summary
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Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. This study is a Phase 2 trial evaluating the efficacy of mocetinostat in patients that have advanced urothelial carcinoma that has specific changes in tumor genes. Patients must have previously received treatment with chemotherapy that included a platinum-containing agent such as cisplatin. The study will enroll in stages, with 15 patients in the first stage. More patients will be added to the study if enough patients having beneficial responses are observed. Mocetinostat will be administered using oral capsules three times each week (eg, Monday, Wednesday and Friday). The study is designed to evaluate whether the number of patients responding to treatment is substantially higher than would be expected with other available treatments.

Detailed Description
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To be eligible for this study, patient tumor testing must demonstrate a genetic alteration resulting in the loss of function of the Histone Acetyltransferase (HAT) family genes, CREBBP and/or EP300, including gene deletions or selected inactivating mutations. If testing has not already been performed, the study will provide for the testing.

Official Title
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An Open-Label, Single-Arm, Phase 2 Study of Mocetinostat in Selected Patients With Inactivating Alterations of Acetyltransferase Genes in Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: Mocetinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of urothelial carcinoma Metastatic or locally advanced disease Prior chemotherapy that included a platinum agent Test results showing genetic change in tumor gene for CREBBP and/or EP300 At least one tumor that can be measured Exclusion Criteria: Uncontrolled tumor in the brain Impaired heart function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mocetinostat<br>Mocetinostat (MGCD0103) oral capsules three times weekly, 70 mg doses in first month, with increase to 90 mg doses if tolerated | Drug: Mocetinostat<br> <br> * Other names: MGCD0103;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing tumor size reduction | Tumors will be measured using radiographic scans. Tumor size reduction and overall disease response will be categorized according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1). | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing adverse events |  | Up to 12 months | 
| Peak blood plasma concentration of mocetinostat |  | Up to 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder, Urothelial, HDAC, MGCD0103, Mocetinostat, CREBBP, EP300, Mirati, MethylGene