Triple Negative Breast CancerPhase 2NCT03057600
Study of CB-839 in Combination w/ Paclitaxel in Participants of African Ancestry and Non-African Ancestry With Advanced Triple Negative Breast Cancer (TNBC)
A Phase 2 study testing Paclitaxel and CB-839 in people with Triple Negative Breast Cancer and TNBC - Triple-Negative Breast Cancer, run by Calithera Biosciences, Inc at 25 sites in United States.
Trial summary
CX-839-007 is an open-label Phase 2 study of the combination of CB-839 with paclitaxel in participants of African ancestry and non-African ancestry with advanced triple negative breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Triple Negative Breast Cancer, TNBC - Triple-Negative Breast Cancer
- What is being tested?
- Paclitaxel and CB-839
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 25 sitesUnited States
- Study dates
- 1 May 2017to 25 Nov 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meets criteria for 1 of the 4 defined study cohorts
- TNBC, defined as estrogen receptor (ER) and progesterone receptor (PR) negative (< 1% by immunohistochemistry) and human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry 0 to 1+ or fluorescence in situ hybridization [FISH] negative)
- Metastatic disease or locally-advanced disease not amenable to curative intent treatment
- Adequate hepatic, renal, cardiac, and hematologic function
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Recovery to baseline or ≤ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version.4.0
Who cannot join
- Known brain metastases or central nervous system (CNS) cancer unless adequately treated with radiotherapy and/or surgery and stable for ≥ 2 mo
- Unable to receive oral medications
- Known hypersensitivity to Cremophor®-based agents
- Major surgery within 28 days of Cycle 1 Day 1
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
University Cancer and Blood Center
Athens, Georgia, 30607
Winship Cancer Institute - Emory University
Atlanta, Georgia, 30332
Weinberg Cancer Institute at Franklin Square
Baltimore, Maryland, 21237
University of Alabama at Brimingham
Birmingham, Alabama, 35294
Charleston Hematology Oncology Associates
Charleston, South Carolina, 29414
Henry Ford Hospital
Detroit, Michigan, 48202
West Cancer Center
Germantown, Tennessee, 38138
Greenville Health System (GHS) Cancer Institute
Greenville, South Carolina, 29605
JTCC at Hackensack UMC
Hackensack, New Jersey, 07601
Baylor College of Medicine
Houston, Texas, 77030
MD Anderson
Houston, Texas, 77030
Northwest Georgia Oncology
Marietta, Georgia, 30060
University of Miami
Miami, Florida, 33176
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of South Alabama, Mitchell Cancer Institute
Mobile, Alabama, 36604
Yale Cancer Center
New Haven, Connecticut, 06511
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
Columbia University
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Magee Womens Hospital - UPMC
Pittsburgh, Pennsylvania, 15213
Saint Louis University
St Louis, Missouri, 63110
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405
Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Georgetown University - Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
Washington Cancer Institute
Washington D.C., District of Columbia, 20010
About this study
Official title: A Multicenter Phase 2 Study of the Glutaminase Inhibitor CB-839 in Combination With Paclitaxel in Patients With Advanced Triple Negative Breast Cancer (TNBC) Including Patients of African Ancestry and Non-African Ancestry
CX-839-007 is an open-label Phase 2 study of the combination of CB-839 with paclitaxel in participants of African ancestry and non-African ancestry with advanced triple negative breast cancer. Multiple single-arm cohorts will be enrolled in which 800 mg twice daily (BID) CB-839 will be administered in combination with the full approved dose of paclitaxel.
Read the detailed description
Participants will be enrolled into 4 cohorts, as follows:
- Cohort 1: patients of African ancestry with 2 or more lines of prior therapy for metastatic disease
- Cohort 2: patients of African ancestry with no prior lines of therapy for metastatic disease
- Cohort 3: same as cohort 1 but in patients of non-African ancestry
- Cohort 4: same as cohort 2 but in patients of non-African ancestry
- Being tested
- Paclitaxel, CB-839
- Keywords
- African ancestry, African American, CB-839, Glutaminase Inhibitor, Glutaminase, TNBC, Tumor Metabolism, Glutamine
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxane
standard weekly paclitaxel in 28-day cycles
CB-839Drug
Also called telaglenastat
CB-839 administered as oral tablets twice daily (BID)
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - African ancestry, 3rd line+ | Experimental | Intervention = Paclitaxel- CB-839 (Pac-CB) combination
1. Participants must self-identify as African ancestry (includes African American).
2. At least 2 prior lines of systemic therapy for advanced/metastatic disease including a taxane.
* Prior taxane (paclitaxel, docetaxel, or nab-paclitaxel) for advanced/metastatic disease is required but must not have been received in the immediate prior line of therapy.
* Systemic neoadjuvant and/or adjuvant therapy is considered a line of therapy for advanced/metastatic disease if the time to recurrence from completion of treatment was ≤ 12 mo. Receives: Drug: Paclitaxel; Drug: CB-839 |
| Cohort 2 - African ancestry, 1st line | Experimental | Intervention = Pac-CB combination
1. Participants must self-identify as African ancestry (includes African American).
2. No prior systemic therapy for advanced or metastatic disease.
* Systemic neoadjuvant or adjuvant therapy, including taxane, is allowed if time to recurrence was > 12 mo. Receives: Drug: Paclitaxel; Drug: CB-839 |
| Cohort 3 - Non-African ancestry, 3rd line+ | Experimental | Intervention = Pac-CB combination
1. Participants do not self-identify as African ancestry.
2. Otherwise have the same criteria as Cohort 1. Receives: Drug: Paclitaxel; Drug: CB-839 |
| Cohort 4 - Non-African ancestry, 1st line | Experimental | Intervention = Pac-CB combination
1. Participants do not self-identify as African ancestry.
2. Otherwise have the same criteria as Cohort 2. Receives: Drug: Paclitaxel; Drug: CB-839 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1criteria:
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessment performed no less than 4 weeks after the criteria for response were first met.
Measured: Maximum duration of follow-up for ORR was 14.8 months.
Secondary outcomes (4)
Progression Free Survival (PFS) as Assessed by Investigator
PFS was defined as time from the first dose date to the earlier of either progression of disease per RECIST v1.1 or death from any cause. The duration of progression-free survival was censored at the date of last radiographic disease if the patient was alive and progression free at the time of analysis data cutoff, disease progression or death occurred after missing data for 2 consecutive radiographic disease assessments, or patient received non-protocol TNBC treatment prior to documentation of disease progression. Kaplan-Meier product-limit estimates. Brookmeyer-Crowley methodology for a non-parametric 95% confidence interval (CI) is used.
Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Maximum duration of follow-up for PFS was 17.0 months.
Overall Survival (OS)
Overall survival is defined as the time from the first dose date to death due to any cause. For patients alive at time of analysis, overall survival will be censored at the time when the patient is last known to be alive.Kaplan-Meier product-limit estimates. Brookmeyer-Crowley methodology for a non-parametric 95% CI is used. Median is defined to be the smallest observed survival time for which the value of the estimated survival function is less than or equal to 0.5.
Measured: Maximum duration of follow-up for OS was 24.1 months.
Duration of Response (DOR)
Duration of response is defined as the time between the first documentation of a confirmed PR or a CR to the first documentation of PD or death, whichever occurs first. The duration of response will be censored at the date of last radiographic disease if the patient is alive and progression free at the time of database lock, disease progression or death occurs after missing data for two consecutive radiographic disease assessments, or patient receives non-protocol TNBC treatment prior to documentation of disease progression.
RECIST v1.1 criteria:
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: Maximum duration of follow-up for DOR was 14.8 months.
Clinical Benefit Rate (CBR)
Clinical Benefit Rate is defined as the percentage of patients with best response of CR, PR, or SD per RECIST v1.1 criteria lasting ≥ 16 weeks for 3rd line + patients and ≥ 24 weeks for 1st line patients. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Maximum duration of follow-up for CBR was 14.8 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2017
- Study start1 May 2017
- Primary completion25 Nov 2019
- Study completion25 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Triple Negative Breast CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be assigned to one of 4 arms depending on the number of prior lines of therapy they have received and whether or not they have African ancestry
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sam Whiting, MD, PhD, Study director, Calithera Biosciences, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03057600
- Sponsor's protocol ID
- CX-839-007
- Status last verified
- Sep 2022
- First submitted
- 10 Feb 2017
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 2 Study of the Glutaminase Inhibitor CB-839 in Combination With Paclitaxel in Patients With Advanced Triple Negative Breast Cancer (TNBC) Including Patients of African Ancestry and Non-African Ancestry
- ClinicalTrials.gov ID
- NCT03057600
- Acronym / sponsor ID
- CX-839-007
- Keywords
- African ancestry, African American, CB-839, Glutaminase Inhibitor, Glutaminase, TNBC, Tumor Metabolism, Glutamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- 1 May 2017 (actual)
- Primary completion
- 25 Nov 2019 (actual)
- Study completion
- 25 Nov 2019 (actual)
- First posted
- 20 Feb 2017 (actual)
- Results
- Posted 28 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CX-839-007 is an open-label Phase 2 study of the combination of CB-839 with paclitaxel in participants of African ancestry and non-African ancestry with advanced triple negative breast cancer. Multiple single-arm cohorts will be enrolled in which 800 mg twice daily (BID) CB-839 will be administered in combination with the full approved dose of paclitaxel.
Detailed description
Participants will be enrolled into 4 cohorts, as follows:
- Cohort 1: patients of African ancestry with 2 or more lines of prior therapy for metastatic disease
- Cohort 2: patients of African ancestry with no prior lines of therapy for metastatic disease
- Cohort 3: same as cohort 1 but in patients of non-African ancestry
- Cohort 4: same as cohort 2 but in patients of non-African ancestry
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Participants will be assigned to one of 4 arms depending on the number of prior lines of therapy they have received and whether or not they have African ancestry
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - African ancestry, 3rd line+ | Experimental | Drug: Paclitaxel, Drug: CB-839Intervention = Paclitaxel- CB-839 (Pac-CB) combination 1. Participants must self-identify as African ancestry (includes African American). 2. At least 2 prior lines of systemic therapy for advanced/metastatic disease including a taxane. * Prior taxane (paclitaxel, docetaxel, or nab-paclitaxel) for advanced/metastatic disease is required but must not have been received in the immediate prior line of therapy. * Systemic neoadjuvant and/or adjuvant therapy is considered a line of therapy for advanced/metastatic disease if the time to recurrence from completion of treatment was ≤ 12 mo. |
| Cohort 2 - African ancestry, 1st line | Experimental | Drug: Paclitaxel, Drug: CB-839Intervention = Pac-CB combination 1. Participants must self-identify as African ancestry (includes African American). 2. No prior systemic therapy for advanced or metastatic disease. * Systemic neoadjuvant or adjuvant therapy, including taxane, is allowed if time to recurrence was > 12 mo. |
| Cohort 3 - Non-African ancestry, 3rd line+ | Experimental | Drug: Paclitaxel, Drug: CB-839Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 1. |
| Cohort 4 - Non-African ancestry, 1st line | Experimental | Drug: Paclitaxel, Drug: CB-839Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Meets criteria for 1 of the 4 defined study cohorts
- TNBC, defined as estrogen receptor (ER) and progesterone receptor (PR) negative (< 1% by immunohistochemistry) and human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry 0 to 1+ or fluorescence in situ hybridization [FISH] negative)
- Metastatic disease or locally-advanced disease not amenable to curative intent treatment
- Adequate hepatic, renal, cardiac, and hematologic function
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Key exclusion criteria (4 listed)
- Known brain metastases or central nervous system (CNS) cancer unless adequately treated with radiotherapy and/or surgery and stable for ≥ 2 mo
- Unable to receive oral medications
- Known hypersensitivity to Cremophor®-based agents
- Major surgery within 28 days of Cycle 1 Day 1
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 |
|---|---|---|
| PaclitaxelAlso: Taxanestandard weekly paclitaxel in 28-day cycles | Drug | Cohort 1 - African ancestry, 3rd line+, Cohort 2 - African ancestry, 1st line, Cohort 3 - Non-African ancestry, 3rd line+, Cohort 4 - Non-African ancestry, 1st line |
| CB-839Also: telaglenastatCB-839 administered as oral tablets twice daily (BID) | Drug | Cohort 1 - African ancestry, 3rd line+, Cohort 2 - African ancestry, 1st line, Cohort 3 - Non-African ancestry, 3rd line+, Cohort 4 - Non-African ancestry, 1st line |
Primary outcome
Overall Response Rate (ORR)
Time frame: Maximum duration of follow-up for ORR was 14.8 months.
ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessment performed no less than 4 weeks after the criteria for response were first met.
4 secondary outcomes
Progression Free Survival (PFS) as Assessed by Investigator
Time frame: Maximum duration of follow-up for PFS was 17.0 months.
Overall Survival (OS)
Time frame: Maximum duration of follow-up for OS was 24.1 months.
Duration of Response (DOR)
Time frame: Maximum duration of follow-up for DOR was 14.8 months.
Clinical Benefit Rate (CBR)
Time frame: Maximum duration of follow-up for CBR was 14.8 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Sam Whiting, MD, PhD study director
Calithera Biosciences, Inc
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel and CB-839 in people with Triple Negative Breast Cancer and TNBC - Triple-Negative Breast Cancer, run by Calithera Biosciences, Inc at 25 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 4 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 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (ORR) (time frame: Maximum duration of follow-up for ORR was 14.8 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 28 Sep 2022.