Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02071862
• Other study ID #: CX-839-001
• Status: Completed
• Phase: Phase 1
• Start date: February 2014
• Est. completion date: March 2019

Study information

• Verified date: February 2020
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• CB-839
CB-839 monotherapy
• Pac-CB
CB-839 in combination with standard dose paclitaxel
• CBE
CB-839 in combination with standard dose everolimus
• CB-Erl
CB-839 in combination with standard dose erlotnib
• CBD
CB-839 in combination with standard dose docetaxel
• CB-Cabo
CB-839 in combination with standard dose cabozantinib

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory School of Medicine	Atlanta	Georgia
United States	NIH - NCI - Center for Cancer Research	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Calithera Biosciences, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood		Study Days 1, 15, and 22
Secondary	Pharmacodynamics: % inhibition of glutaminase in blood		Study Days 1 and 15
Secondary	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

External Links

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