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NCT Number: NCT02071862

Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

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.

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Key information

Conditions

Solid Tumors Adenocarcinoma Adenoma Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fumarate Hydratase (FH)-Deficient Tumors Kidney Diseases Kidney Neoplasms Lung Diseases Lung Neoplasms Male Urogenital Diseases Mesothelioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Non Small Cell Lung Cancer Renal Cell Carcinoma Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST) Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors Thoracic Neoplasms Triple Negative Breast Neoplasms Triple-negative Breast Cancer Tumors Harboring Amplifications in the cMyc Gene Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CB-839

Drug

CB-839 monotherapy

Other names: Glutaminase Inhibitor

Pac-CB

Drug

CB-839 in combination with standard dose paclitaxel

Other names: combo CB-839 and Paclitaxel

CBE

Drug

CB-839 in combination with standard dose everolimus

Other names: combo CB-839 and everolimus

CB-Erl

Drug

CB-839 in combination with standard dose erlotnib

Other names: combo CB-839 and erlotnib

CBD

Drug

CB-839 in combination with standard dose docetaxel

Other names: combo CB-839 and docetaxel

CB-Cabo

Drug

CB-839 in combination with standard dose cabozantinib

Other names: combo CB-839 and cabozantinib

Primary outcomes

  1. Safety and tolerability of CB-839: Incidence of adverse events

    Time frame: Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months

Secondary outcomes

  1. Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood

    Time frame: Study Days 1, 15, and 22

  2. Pharmacodynamics: % inhibition of glutaminase in blood

    Time frame: Study Days 1 and 15

  3. Clinical activity: Change in tumor volume from baseline

    Time frame: Every 9 weeks until disease progression or unacceptable toxicity, assessed for an expected average of 6 months

Sponsors and collaborators

Lead sponsor

Calithera Biosciences, Inc

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2019
Study completion
2019
First posted
Feb 26, 2014
Registry last updated
Jul 20, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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