Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE February 14, 2014
First Posted Date  ICMJE February 26, 2014
Last Update Posted Date July 19, 2018
Study Start Date  ICMJE February 2014
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2014)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02071862 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2014)
  • Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood [ Time Frame: Study Days 1, 15, and 22 ]
  • Pharmacodynamics: % inhibition of glutaminase in blood [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
  • Drug: CBE
    CB-839 in combination with standard dose everolimus
    Other Name: combo CB-839 and everolimus
  • Drug: CB-Erl
    CB-839 in combination with standard dose erlotnib
    Other Name: combo CB-839 and erlotnib
  • Drug: CBD
    CB-839 in combination with standard dose docetaxel
    Other Name: combo CB-839 and docetaxel
  • Drug: CB-Cabo
    CB-839 in combination with standard dose cabozantinib
    Other Name: combo CB-839 and cabozantinib
Study Arms  ICMJE
  • 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
    Intervention: Drug: CB-839
  • 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
    Interventions:
    • Drug: CB-839
    • Drug: Pac-CB
  • 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
    Interventions:
    • Drug: CB-839
    • Drug: CBE
  • 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
    Interventions:
    • Drug: CB-839
    • Drug: CB-Erl
  • 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
    Interventions:
    • Drug: CB-839
    • Drug: CBD
  • 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
    Intervention: Drug: CB-Cabo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 27, 2016)
205
Original Estimated Enrollment  ICMJE
 (submitted: February 24, 2014)
100
Estimated Study Completion Date  ICMJE September 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02071862
Other Study ID Numbers  ICMJE CX-839-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Calithera Biosciences, Inc
Study Sponsor  ICMJE Calithera Biosciences, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Samuel Whiting, MD, PhD Calithera Biosciences, Inc
PRS Account Calithera Biosciences, Inc
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP