Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
- Conditions
- Solid TumorsTriple-Negative Breast CancerNon Small Cell Lung CancerRenal Cell CarcinomaMesotheliomaSuccinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal TumorsTumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 MutationsFumarate Hydratase (FH)-Deficient TumorsSuccinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST)Tumors Harboring Amplifications in the cMyc Gene
- Interventions
- Registration Number
- NCT02071862
- Lead Sponsor
- Calithera Biosciences, Inc
- Brief 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, H) tumors harboring mutations in isocitrate dehydrogenase-1 (IDH1) or IDH2, and I) cMyc mutation tumors.
As an extension of Parts 1 \& 2, patients will be treated with CB-839 in combination with standard chemotherapy. Combination groups include: Pac-CB, CBE, CB-Erl, CBD, and CB-Cabo. Pac-CB: patients with locally-advanced or metastatic TNBC will be treated with paclitaxel and CB-839. CBE: patients with advanced clear cell RCC or papillary RCC will be treated with everolimus in combination with CB-839. CB-Erl: patients with advanced NSCLC lacking the T790M EGFR mutation will be treated with erlotinib and CB-839. CBD: patients with NSCLC harboring KRAS mutation will be treated with docetaxel and CB-839. CB-Cabo: patients with histologically confirmed diagnosis of locally-advanced, inoperable or metastatic RCC treated with cabozantinib in combination with 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 210
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pac-CB CB-839 CB-839 administered as oral capsules twice daily (BID) in combination with standard dose paclitaxel in 28-day cycles until disease progression or unacceptable toxicity CBD CB-839 CB-839 administered as oral capsules twice daily (BID) in combination with standard dose docetaxel in 21-day cycles until disease progression or unacceptable toxicity CBE CB-839 CB-839 administered as oral capsules twice daily (BID) in combination with standard dose everolimus in 28-day cycles until disease progression or unacceptable toxicity Pac-CB Pac-CB CB-839 administered as oral capsules twice daily (BID) in combination with standard dose paclitaxel in 28-day cycles until disease progression or unacceptable toxicity CB-839 CB-839 CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity CB-Erl CB-839 CB-839 administered as oral capsules twice daily (BID) in combination with standard dose erlotnib in 28-day cycles until disease progression or unacceptable toxicity CBE CBE CB-839 administered as oral capsules twice daily (BID) in combination with standard dose everolimus in 28-day cycles until disease progression or unacceptable toxicity CB-Erl CB-Erl CB-839 administered as oral capsules twice daily (BID) in combination with standard dose erlotnib in 28-day cycles until disease progression or unacceptable toxicity CB-Cabo CB-Cabo CB-839 administered as oral capsules twice daily (BID) in combination with standard dose cabozantinib in 28-day cycles until disease progression or unacceptable toxicity CBD CBD CB-839 administered as oral capsules twice daily (BID) in combination with standard dose docetaxel in 21-day cycles until disease progression or unacceptable toxicity
- Primary Outcome Measures
Name Time Method Safety and tolerability of CB-839: Incidence of adverse events Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months
- Secondary Outcome Measures
Name Time Method Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood Study Days 1, 15, and 22 Pharmacodynamics: % inhibition of glutaminase in blood Study Days 1 and 15 Clinical activity: Change in tumor volume from baseline Every 9 weeks until disease progression or unacceptable toxicity, assessed for an expected average of 6 months
Trial Locations
- Locations (13)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Winship Cancer Institute of Emory School of Medicine
🇺🇸Atlanta, Georgia, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
NIH - NCI - Center for Cancer Research
🇺🇸Bethesda, Maryland, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Pennsylvania, Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States