Trial | NCT02071862  Report issue

Title

Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
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

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    210
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.
Study Started
Feb 28
2014
Primary Completion
Mar 31
2019
Study Completion
Mar 31
2019
Last Update
Jul 20
2022

Drug CB-839

CB-839 monotherapy

  • Other names: Glutaminase Inhibitor

Drug Pac-CB

CB-839 in combination with standard dose paclitaxel

  • Other names: combo CB-839 and Paclitaxel

Drug CBE

CB-839 in combination with standard dose everolimus

  • Other names: combo CB-839 and everolimus

Drug CB-Erl

CB-839 in combination with standard dose erlotnib

  • Other names: combo CB-839 and erlotnib

Drug CBD

CB-839 in combination with standard dose docetaxel

  • Other names: combo CB-839 and docetaxel

Drug CB-Cabo

CB-839 in combination with standard dose cabozantinib

  • Other names: combo CB-839 and cabozantinib

CB-839 Experimental

CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity

Pac-CB Experimental

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

CBE Experimental

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 Experimental

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

CBD Experimental

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

CB-Cabo Experimental

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

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
No Results Posted