Clinical trial NCT02236195: Study of Mocetinostat in Patients With Urothelial Carcinoma Having Inactivating Alterations of Specific Genes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Keywords: Urothelial
Bladder
HDAC
MGCD0103
Mocetinostat
CREBBP
EP300
Mirati
MethylGene
Lead sponsor: Mirati Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-10
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients experiencing tumor size reduction
timeFrame: Up to 4 months
Secondary outcomes:
measure: Number of patients experiencing adverse events
timeFrame: Up to 12 months
measure: Peak blood plasma concentration of mocetinostat
timeFrame: Up to 48 hours
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
References:
citation: Grivas P, Mortazavi A, Picus J, Hahn NM, Milowsky MI, Hart LL, Alva A, Bellmunt J, Pal SK, Bambury RM, O'Donnell PH, Gupta S, Guancial EA, Sonpavde GP, Faltaos D, Potvin D, Christensen JG, Chao RC, Rosenberg JE. Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes. Cancer. 2019 Feb 15;125(4):533-540. doi: 10.1002/cncr.31817. Epub 2018 Dec 20.