Study of CB-839 in Combination w/ Paclitaxel in Participants of African Ancestry and Non-African Ancestry With Advanced Triple Negative Breast Cancer (TNBC)

Triple Negative Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03057600
• Other study ID #: CX-839-007
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2017
• Est. completion date: November 25, 2019

Study information

• Verified date: September 2022
• Source: Calithera Biosciences, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 25, 2019
• Est. primary completion date: November 25, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Paclitaxel
standard weekly paclitaxel in 28-day cycles
• CB-839
CB-839 administered as oral tablets twice daily (BID)

Locations

Country	Name	City	State
United States	University Cancer and Blood Center	Athens	Georgia
United States	Winship Cancer Institute - Emory University	Atlanta	Georgia
United States	Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland
United States	University of Alabama at Brimingham	Birmingham	Alabama
United States	Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Henry Ford Hospital	Detroit	Michigan
United States	West Cancer Center	Germantown	Tennessee
United States	Greenville Health System (GHS) Cancer Institute	Greenville	South Carolina
United States	JTCC at Hackensack UMC	Hackensack	New Jersey
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson	Houston	Texas
United States	Northwest Georgia Oncology	Marietta	Georgia
United States	University of Miami	Miami	Florida
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of South Alabama, Mitchell Cancer Institute	Mobile	Alabama
United States	Yale Cancer Center	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Magee Womens Hospital - UPMC	Pittsburgh	Pennsylvania
United States	Saint Louis University	Saint Louis	Missouri
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Georgetown University - Lombardi Comprehensive Cancer Center	Washington	District of Columbia
United States	Washington Cancer Institute	Washington	District of Columbia

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	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.	Maximum duration of follow-up for ORR was 14.8 months.
Secondary	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.	Maximum duration of follow-up for PFS was 17.0 months.
Secondary	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.	Maximum duration of follow-up for OS was 24.1 months.
Secondary	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.	Maximum duration of follow-up for DOR was 14.8 months.
Secondary	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.	Maximum duration of follow-up for CBR was 14.8 months.

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