Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

July 18, 2022 updated by: Calithera Biosciences, Inc

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

210

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • UCSF Helen Diller Family Comprehensive Cancer Center
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory School of Medicine
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • NIH - NCI - Center for Cancer Research
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania, Abramson Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: CB-839
CB-839 monotherapy
Other Names:
  • Glutaminase Inhibitor
Experimental: 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
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
Experimental: 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
Drug: CB-839
CB-839 monotherapy
Other Names:
  • Glutaminase Inhibitor
Drug: CBE
CB-839 in combination with standard dose everolimus
Other Names:
  • combo CB-839 and everolimus
Experimental: 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
Drug: CB-839
CB-839 monotherapy
Other Names:
  • Glutaminase Inhibitor
Drug: CB-Erl
CB-839 in combination with standard dose erlotnib
Other Names:
  • combo CB-839 and erlotnib
Experimental: 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
Drug: CB-839
CB-839 monotherapy
Other Names:
  • Glutaminase Inhibitor
Drug: CBD
CB-839 in combination with standard dose docetaxel
Other Names:
  • combo CB-839 and docetaxel
Experimental: 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
Drug: CB-Cabo
CB-839 in combination with standard dose cabozantinib
Other Names:
  • combo CB-839 and cabozantinib

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Time Frame: Study Days 1, 15, and 22
Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Time Frame: Study Days 1 and 15
Study Days 1 and 15
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
Every 9 weeks until disease progression or unacceptable toxicity, assessed for an expected average of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Calithera Biosciences, Inc

Investigators

  • Study Director: Samuel Whiting, MD, PhD, Calithera Biosciences, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

March 1, 2019

Study Completion (Actual)

March 1, 2019

Study Registration Dates

First Submitted

February 14, 2014

First Submitted That Met QC Criteria

February 24, 2014

First Posted (Estimate)

February 26, 2014

Study Record Updates

Last Update Posted (Actual)

July 20, 2022

Last Update Submitted That Met QC Criteria

July 18, 2022

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CX-839-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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