Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

NCT02071862 | Completed Phase 1

• 1 other identifier: CX-839-001
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 13

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.

Conditions

Solid Tumors; Triple-Negative Breast Cancer; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Mesothelioma; Fumarate Hydratase (FH)-Deficient Tumors; Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST); Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors; Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations; Tumors Harboring Amplifications in the cMyc Gene

Keywords

Tumor metabolism; Glutaminase; Glutamine; Tricarboxylic acid (TCA) cycle

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (6)

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

Drug: CB-839

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

Drug: CB-839; Drug: Pac-CB

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

Drug: CB-839; Drug: CBE

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

Drug: CB-839; Drug: CB-Erl

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

Drug: CB-839; Drug: CBD

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

Drug: CB-Cabo

Interventions

CB-839 DRUG

CB-839 monotherapy

Also known as: Glutaminase Inhibitor

CB-839; CB-Erl; CBD; CBE; Pac-CB

Pac-CB DRUG

CB-839 in combination with standard dose paclitaxel

Also known as: combo CB-839 and Paclitaxel

Pac-CB

CBE DRUG

CB-839 in combination with standard dose everolimus

Also known as: combo CB-839 and everolimus

CBE

CB-Erl DRUG

CB-839 in combination with standard dose erlotnib

Also known as: combo CB-839 and erlotnib

CB-Erl

CBD DRUG

CB-839 in combination with standard dose docetaxel

Also known as: combo CB-839 and docetaxel

CBD

CB-Cabo DRUG

CB-839 in combination with standard dose cabozantinib

Also known as: combo CB-839 and cabozantinib

CB-Cabo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (13)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Winship Cancer Institute of Emory School of Medicine

Atlanta, Georgia, 30322, United States

Location

NIH - NCI - Center for Cancer Research

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Mesothelioma

Interventions

CB-839; Paclitaxel; Everolimus; Docetaxel; cabozantinib

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenoma; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Sirolimus; Macrolides; Lactones

Study Officials

• Samuel Whiting, MD, PhD

  Calithera Biosciences, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 26, 2014
• Study Start: February 1, 2014
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: July 20, 2022

Record last verified: 2020-02

Locations

US (13)