Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
Status: | Active, not recruiting |
---|---|
Conditions: | Breast Cancer, Lung Cancer, Lung Cancer, Lung Cancer, Cancer, Cancer, Cancer, Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 7/21/2018 |
Start Date: | February 2014 |
End Date: | September 2019 |
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
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.
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.
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
We found this trial at
13
sites
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185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Othon Iliopoulos, MD
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330 Brookline Ave
Boston, Massachusetts 02215
Boston, Massachusetts 02215
617-667-7000
Principal Investigator: James W Mier, MD
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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1600 Divisadero Street
San Francisco, California 94115
San Francisco, California 94115
888.689.8273
Principal Investigator: Pamela Munster
UCSF Helen Diller Family Comprehensive Cancer Center UCSF’s long tradition of excellence in cancer research...
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Atlanta, Georgia 30322
Principal Investigator: Taofeek K Owonikoko, MD, PhD
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450 Brookline Ave
Boston, Massachusetts 2215
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: George D Demetri, MD
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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1515 Holcombe Blvd
Houston, Texas 77030
Houston, Texas 77030
713-792-2121
Principal Investigator: Funda Meric-Bernstam, MD
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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250 25th Ave N, Ste 100
Nashville, Tennessee 37023
Nashville, Tennessee 37023
615-320-5090
Principal Investigator: Jeffrey R Infante, MD
Tennessee Oncology, PLLC Since 1976 Tennessee Oncology has been providing quality cancer care. In 2013,...
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630 W 168th St
New York, New York
New York, New York
212-305-2862
Principal Investigator: Gary K Schwartz, MD
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Philadelphia, Pennsylvania 19104
Principal Investigator: Angela M DeMichele, MD MSCE
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300 Pasteur Dr
Stanford, California 94305
Stanford, California 94305
(650) 723-4000
Principal Investigator: Melinda L Telli, MD
Stanford Univ Med Ctr The Medical Center is uniquely advantaged by its location on the...
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