Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Calithera Biosciences, Inc
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc
ClinicalTrials.gov Identifier:
NCT02071862
First received: February 14, 2014
Last updated: August 7, 2014
Last verified: August 2014
  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 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, and D) Mesothelioma. 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.


Condition Intervention Phase
Solid Tumors
Triple-Negative Breast Cancer
Non Small Cell Lung Cancer
Renal Cell Carcinoma
Mesothelioma
Drug: CB-839
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Glutaminase Inhibitor CB-839 in Patients With Advanced and/or Treatment-Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Calithera Biosciences, Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood [ Time Frame: Study Days 1, 15, and 22 ] [ Designated as safety issue: No ]
  • Pharmacodynamics: % inhibition of glutaminase in blood [ Time Frame: Study Days 1 and 15 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: February 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CB-839
CB-839 administered as oral capsules three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity
Drug: CB-839
Glutaminase inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 are known to 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02071862

Contacts
Contact: Robin King (615) 329-7346 robin.king@scri-innovations.com
Contact: Sara Ramsey (615) 329-7240 sara.ramsey@scri-innovations.com

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Pamela Munster         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Principal Investigator: Melinda L Telli, MD         
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Principal Investigator: Manish R Patel, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York City, New York, United States, 10065
Principal Investigator: James J Harding, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Angela M DeMichele, MD MSCE         
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Jeffrey R Infante, MD         
Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
Study Director: Mai H Le, MD Calithera Biosciences
  More Information

Additional Information:
No publications provided

Responsible Party: Calithera Biosciences, Inc
ClinicalTrials.gov Identifier: NCT02071862     History of Changes
Other Study ID Numbers: CX-839-001
Study First Received: February 14, 2014
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Calithera Biosciences, Inc:
Tumor metabolism
Glutaminase
Glutamine

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Lung Neoplasms
Mesothelioma
Neoplasms, Mesothelial
Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Adenoma

ClinicalTrials.gov processed this record on September 14, 2014