©2022 Stanford Medicine
Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
Not Recruiting
Trial ID: NCT02071862
Purpose
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.
Official Title
Ph1 Study of the Safety, PK, and PDn of Escalating Oral Doses of the Glutaminase Inhibitor CB-839, as a Single Agent and in Combination With Standard Chemotherapy in Patients With Advanced and/or Treatment-Refractory Solid Tumors
Stanford Investigator(s)
Alice C. Fan
Assistant Professor of Medicine (Oncology) and, by courtesy, of Urology
Melinda L. Telli, M.D.
Associate Professor of Medicine (Oncology)
Joel Neal, MD, PhD
Associate Professor of Medicine (Oncology)
Heather Wakelee
Professor of Medicine (Oncology)
Eligibility
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
Intervention(s):
drug: CB-839
drug: Pac-CB
drug: CBE
drug: CB-Erl
drug: CBD
drug: CB-Cabo
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
CCTO
650-498-7061