Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
Conditions
Solid Tumors - Triple-Negative Breast Cancer - Non Small Cell Lung Cancer - Renal Cell Carcinoma - Mesothelioma - Fumarate Hydratase (FH)-Deficient Tumors - Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST) - Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors - Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations
Conditions: official terms
Carcinoma, Non-Small-Cell Lung - Carcinoma, Renal Cell - Gastrointestinal Stromal Tumors - Mesothelioma - Neoplasms - Triple Negative Breast Neoplasms
Conditions: Keywords
Tumor metabolism, Glutaminase, Glutamine, Tricarboxylic acid (TCA) cycle
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: CB-839
Type: Drug
Overall Status
Recruiting
Summary
Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with solid tumors.

This study is an open-label Phase 1 evaluation of CB-839 in patients with advanced solid tumors. The study will be conducted in 2 parts. Part 1 is a dose escalation study enrolling patients with locally-advanced, metastatic and/or refractory solid tumors to receive CB-839 capsules orally twice or three times daily.

In Part 2, patients with each of the following diseases will be enrolled: A) Triple-Negative Breast Cancer, B) Non-Small Cell Lung Cancer (adenocarcinoma), C) Renal Cell Cancer, D) Mesothelioma, E) Fumarate hydratase (FH)-deficient tumors, F) Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST), G) SDH-deficient non-GIST tumors, and H) tumors harboring mutations in isocitrate dehydrogenase-1 (IDH1) or IDH2.

As an extension of Part 2, patients with locally-advanced or metastatic TNBC will be enrolled to evaluate the safety and tolerability of standard dose paclitaxel and CB-839.

All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion criteria

- Advanced malignancy that is relapsed and/or refractory to all available therapies that will confer clinical benefit. Newly diagnosed patients who refuse standard treatment regimens are also eligible

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

- Life Expectancy of at least 3 months

- Adequate hepatic, renal, cardiac, and hematologic function

- Measurable disease by RECIST criteria

- Ability to provide written informed consent in accordance with federal, local, and institutional guidelines

Exclusion Criteria

- Any other current or previous malignancy

- Chemotherapy, radiation therapy, hormonal therapy, immunotherapy or biological therapy, or investigational agent within 21 days

- Unable to receive medications oral medications

- Major surgery within 28 days before Cycle 1 Day 1

- Active infection requiring within 2 weeks prior to first dose of study drug

- Patients who have HIV, Hepatitis A, B or C or CMV reactivation

- Significant neurotoxicity/neuropathy (Grade 3 or higher) within 14 days of first dose of study drug

- Conditions that could interfere with treatment or protocol-related procedures
Locations
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Status: Recruiting
Stanford University Medical Center
Stanford, California, United States
Status: Recruiting
Florida Cancer Specialists
Sarasota, Florida, United States
Status: Recruiting
Winship Cancer Institute of Emory School of Medicine
Atlanta, Georgia, United States
Status: Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Status: Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Status: Recruiting
Massachusetts General Hospital
Boston, Massachusetts, United States
Status: Recruiting
Memorial Sloan Kettering Cancer Center
New York City, New York, United States
Status: Recruiting
Columbia University Medical Center
New York, New York, United States
Status: Recruiting
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Status: Recruiting
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
Status: Recruiting
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Status: Recruiting
Start Date
February 2014
Completion Date
March 2016
Sponsors
Calithera Biosciences, Inc
Source
Calithera Biosciences, Inc
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page