Solid TumorsPhase 1NCT02071862
Study of the Glutaminase Inhibitor CB-839 in Solid Tumors
A Phase 1 study testing CB-839, Pac-CB and CBE in people with Solid Tumors and Triple-Negative Breast Cancer, run by Calithera Biosciences, Inc at 13 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Triple-Negative Breast Cancer, Non Small Cell Lung Cancer
- What is being tested?
- CB-839, Pac-CB and CBE
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 13 sitesUnited States
- Study dates
- Feb 2014to Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Winship Cancer Institute of Emory School of Medicine
Atlanta, Georgia, 30322
NIH - NCI - Center for Cancer Research
Bethesda, Maryland, 20892
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143
Florida Cancer Specialists
Sarasota, Florida, 34232
Stanford University Medical Center
Stanford, California, 94305
About this study
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
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.
Read more
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.
- Conditions
- Solid Tumors, Triple-Negative Breast Cancer, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Mesothelioma, Fumarate Hydratase (FH)-Deficient Tumors
- Being tested
- CB-839, Pac-CB, CBE, CB-Erl, CBD
- Keywords
- Tumor metabolism, Glutaminase, Glutamine, Tricarboxylic acid (TCA) cycle
- Medical subject headings
- Triple Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-839Drug
Also called Glutaminase Inhibitor
CB-839 monotherapy
Pac-CBDrug
Also called combo CB-839 and Paclitaxel
CB-839 in combination with standard dose paclitaxel
CBEDrug
Also called combo CB-839 and everolimus
CB-839 in combination with standard dose everolimus
CB-ErlDrug
Also called combo CB-839 and erlotnib
CB-839 in combination with standard dose erlotnib
CBDDrug
Also called combo CB-839 and docetaxel
CB-839 in combination with standard dose docetaxel
CB-CaboDrug
Also called combo CB-839 and cabozantinib
CB-839 in combination with standard dose cabozantinib
| Study group | Role | What they receive |
|---|---|---|
| CB-839 | Experimental | CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity Receives: Drug: CB-839 |
| Pac-CB | Experimental | 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 Receives: Drug: CB-839; Drug: Pac-CB |
| CBE | Experimental | 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 Receives: Drug: CB-839; Drug: CBE |
| CB-Erl | Experimental | 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 Receives: Drug: CB-839; Drug: CB-Erl |
| CBD | Experimental | 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 Receives: Drug: CB-839; Drug: CBD |
| CB-Cabo | Experimental | 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 Receives: Drug: CB-Cabo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of CB-839: Incidence of adverse events
Measured: Every 21 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months
Secondary outcomes (3)
Pharmacokinetics: Area under the Curve (AUC) of CB-839 concentration in blood
Measured: Study Days 1, 15, and 22
Pharmacodynamics: % inhibition of glutaminase in blood
Measured: Study Days 1 and 15
Clinical activity: Change in tumor volume from baseline
Measured: Every 9 weeks until disease progression or unacceptable toxicity, assessed for an expected average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Samuel Whiting, MD, PhD, Study director, Calithera Biosciences, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02071862
- Sponsor's protocol ID
- CX-839-001
- Status last verified
- Feb 2020
- First submitted
- 14 Feb 2014
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02071862
- Acronym / sponsor ID
- CX-839-001
- Conditions
- Solid Tumors, Triple-Negative Breast Cancer, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Mesothelioma, Fumarate Hydratase (FH)-Deficient Tumors
- Keywords
- Tumor metabolism, Glutaminase, Glutamine, Tricarboxylic acid (TCA) cycle
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 26 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| CB-839 | Experimental | Drug: CB-839CB-839 administered as oral capsules two (BID) or three times daily (TID) in 21-day cycles until disease progression or unacceptable toxicity |
| Pac-CB | Experimental | Drug: CB-839, Drug: Pac-CBCB-839 administered as oral capsules twice daily (BID) in combination with standard dose paclitaxel in 28-day cycles until disease progression or unacceptable toxicity |
| CBE | Experimental | Drug: CB-839, Drug: CBECB-839 administered as oral capsules twice daily (BID) in combination with standard dose everolimus in 28-day cycles until disease progression or unacceptable toxicity |
| CB-Erl | Experimental | Drug: CB-839, Drug: CB-ErlCB-839 administered as oral capsules twice daily (BID) in combination with standard dose erlotnib in 28-day cycles until disease progression or unacceptable toxicity |
| CBD | Experimental | Drug: CB-839, Drug: CBDCB-839 administered as oral capsules twice daily (BID) in combination with standard dose docetaxel in 21-day cycles until disease progression or unacceptable toxicity |
| CB-Cabo | Experimental | Drug: CB-CaboCB-839 administered as oral capsules twice daily (BID) in combination with standard dose cabozantinib in 28-day cycles until disease progression or unacceptable toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CB-839Also: Glutaminase InhibitorCB-839 monotherapy | Drug | CB-839, CB-Erl, CBD, CBE, Pac-CB |
| Pac-CBAlso: combo CB-839 and PaclitaxelCB-839 in combination with standard dose paclitaxel | Drug | Pac-CB |
| CBEAlso: combo CB-839 and everolimusCB-839 in combination with standard dose everolimus | Drug | CBE |
| CB-ErlAlso: combo CB-839 and erlotnibCB-839 in combination with standard dose erlotnib | Drug | CB-Erl |
| CBDAlso: combo CB-839 and docetaxelCB-839 in combination with standard dose docetaxel | Drug | CBD |
| CB-CaboAlso: combo CB-839 and cabozantinibCB-839 in combination with standard dose cabozantinib | Drug | CB-Cabo |
Primary outcome
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
3 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel Whiting, MD, PhD study director
Calithera Biosciences, Inc
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CB-839, Pac-CB and CBE in people with Solid Tumors and Triple-Negative Breast Cancer, run by Calithera Biosciences, Inc at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022.