Study of CB-839 in Combination w/ Paclitaxel in Participants of African Ancestry and Non-African Ancestry With Advanced Triple Negative Breast Cancer (TNBC)
|
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: NCT03057600 |
|
Recruitment Status :
Completed
First Posted : February 20, 2017
Results First Posted : September 28, 2022
Last Update Posted : September 28, 2022
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Triple Negative Breast Cancer TNBC - Triple-Negative Breast Cancer | Drug: Paclitaxel Drug: CB-839 | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 52 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention 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) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | May 1, 2017 |
| Actual Primary Completion Date : | November 25, 2019 |
| Actual Study Completion Date : | November 25, 2019 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Cohort 1 - African ancestry, 3rd line+
Intervention = Paclitaxel- CB-839 (Pac-CB) combination
|
Drug: Paclitaxel
standard weekly paclitaxel in 28-day cycles
Other Name: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID)
Other Name: telaglenastat |
|
Experimental: Cohort 2 - African ancestry, 1st line
Intervention = Pac-CB combination
|
Drug: Paclitaxel
standard weekly paclitaxel in 28-day cycles
Other Name: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID)
Other Name: telaglenastat |
|
Experimental: Cohort 3 - Non-African ancestry, 3rd line+
Intervention = Pac-CB combination
|
Drug: Paclitaxel
standard weekly paclitaxel in 28-day cycles
Other Name: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID)
Other Name: telaglenastat |
|
Experimental: Cohort 4 - Non-African ancestry, 1st line
Intervention = Pac-CB combination
|
Drug: Paclitaxel
standard weekly paclitaxel in 28-day cycles
Other Name: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID)
Other Name: telaglenastat |
- 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.
- Progression Free Survival (PFS) as Assessed by Investigator [ Time Frame: Maximum duration of follow-up for PFS was 17.0 months. ]
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.
- Overall Survival (OS) [ Time Frame: Maximum duration of follow-up for OS was 24.1 months. ]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.
- Duration of Response (DOR) [ Time Frame: Maximum duration of follow-up for DOR was 14.8 months. ]
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.
- Clinical Benefit Rate (CBR) [ Time Frame: Maximum duration of follow-up for CBR was 14.8 months. ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- 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
Key Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03057600
Show 25 study locations
| Study Director: | Sam Whiting, MD, PhD | Calithera Biosciences, Inc |
Documents provided by Calithera Biosciences, Inc:
| Responsible Party: | Calithera Biosciences, Inc |
| ClinicalTrials.gov Identifier: | NCT03057600 |
| Other Study ID Numbers: |
CX-839-007 |
| First Posted: | February 20, 2017 Key Record Dates |
| Results First Posted: | September 28, 2022 |
| Last Update Posted: | September 28, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
African ancestry African American CB-839 Glutaminase Inhibitor |
Glutaminase TNBC Tumor Metabolism Glutamine |
|
Breast Neoplasms Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |