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Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

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ClinicalTrials.gov Identifier: NCT02071862
Recruitment Status : Active, not recruiting
First Posted : February 26, 2014
Last Update Posted : July 19, 2018
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

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.


Condition or disease Intervention/treatment Phase
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 Drug: CB-839 Drug: Pac-CB Drug: CBE Drug: CB-Erl Drug: CBD Drug: CB-Cabo Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 205 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : February 2014
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : September 2019


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 Name: 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 Name: Glutaminase Inhibitor

Drug: Pac-CB
CB-839 in combination with standard dose paclitaxel
Other Name: 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 Name: Glutaminase Inhibitor

Drug: CBE
CB-839 in combination with standard dose everolimus
Other Name: 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 Name: Glutaminase Inhibitor

Drug: CB-Erl
CB-839 in combination with standard dose erlotnib
Other Name: 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 Name: Glutaminase Inhibitor

Drug: CBD
CB-839 in combination with standard dose docetaxel
Other Name: 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 Name: combo CB-839 and cabozantinib




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02071862


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

Additional Information:
Responsible Party: Calithera Biosciences, Inc
ClinicalTrials.gov Identifier: NCT02071862     History of Changes
Other Study ID Numbers: CX-839-001
First Posted: February 26, 2014    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018

Keywords provided by Calithera Biosciences, Inc:
Tumor metabolism
Glutaminase
Glutamine
Tricarboxylic acid (TCA) cycle

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