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

Primary Purpose

Triple Negative Breast Cancer, TNBC - Triple-Negative Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Paclitaxel
CB-839
Sponsored by
Calithera Biosciences, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring African ancestry, African American, CB-839, Glutaminase Inhibitor, Glutaminase, TNBC, Tumor Metabolism, Glutamine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Brimingham
  • University of South Alabama, Mitchell Cancer Institute
  • Yale Cancer Center
  • Georgetown University - Lombardi Comprehensive Cancer Center
  • Washington Cancer Institute
  • University of Miami
  • Moffitt Cancer Center and Research Institute
  • University Cancer and Blood Center
  • Winship Cancer Institute - Emory University
  • Northwest Georgia Oncology
  • Ochsner Clinic Foundation
  • Weinberg Cancer Institute at Franklin Square
  • Henry Ford Hospital
  • Saint Louis University
  • JTCC at Hackensack UMC
  • Columbia University
  • University of Pennsylvania
  • Magee Womens Hospital - UPMC
  • Charleston Hematology Oncology Associates
  • Greenville Health System (GHS) Cancer Institute
  • West Cancer Center
  • Baylor College of Medicine
  • MD Anderson
  • Northwest Medical Specialties, PLLC
  • Froedtert and the Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

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

Arm Description

Intervention = Paclitaxel- CB-839 (Pac-CB) combination Participants must self-identify as African ancestry (includes African American). 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.

Intervention = Pac-CB combination Participants must self-identify as African ancestry (includes African American). 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.

Intervention = Pac-CB combination Participants do not self-identify as African ancestry. Otherwise have the same criteria as Cohort 1.

Intervention = Pac-CB combination Participants do not self-identify as African ancestry. Otherwise have the same criteria as Cohort 2.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 10, 2017
Last Updated
September 19, 2022
Sponsor
Calithera Biosciences, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT03057600
Brief Title
Study of CB-839 in Combination w/ Paclitaxel in Participants of African Ancestry and Non-African Ancestry With Advanced Triple Negative Breast Cancer (TNBC)
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
November 25, 2019 (Actual)
Study Completion Date
November 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Calithera Biosciences, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer, TNBC - Triple-Negative Breast Cancer
Keywords
African ancestry, African American, CB-839, Glutaminase Inhibitor, Glutaminase, TNBC, Tumor Metabolism, Glutamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 - African ancestry, 3rd line+
Arm Type
Experimental
Arm Description
Intervention = Paclitaxel- CB-839 (Pac-CB) combination Participants must self-identify as African ancestry (includes African American). 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.
Arm Title
Cohort 2 - African ancestry, 1st line
Arm Type
Experimental
Arm Description
Intervention = Pac-CB combination Participants must self-identify as African ancestry (includes African American). 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.
Arm Title
Cohort 3 - Non-African ancestry, 3rd line+
Arm Type
Experimental
Arm Description
Intervention = Pac-CB combination Participants do not self-identify as African ancestry. Otherwise have the same criteria as Cohort 1.
Arm Title
Cohort 4 - Non-African ancestry, 1st line
Arm Type
Experimental
Arm Description
Intervention = Pac-CB combination Participants do not self-identify as African ancestry. Otherwise have the same criteria as Cohort 2.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxane
Intervention Description
standard weekly paclitaxel in 28-day cycles
Intervention Type
Drug
Intervention Name(s)
CB-839
Other Intervention Name(s)
telaglenastat
Intervention Description
CB-839 administered as oral tablets twice daily (BID)
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Maximum duration of follow-up for ORR was 14.8 months.
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) as Assessed by Investigator
Description
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.
Time Frame
Maximum duration of follow-up for PFS was 17.0 months.
Title
Overall Survival (OS)
Description
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.
Time Frame
Maximum duration of follow-up for OS was 24.1 months.
Title
Duration of Response (DOR)
Description
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.
Time Frame
Maximum duration of follow-up for DOR was 14.8 months.
Title
Clinical Benefit Rate (CBR)
Description
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.
Time Frame
Maximum duration of follow-up for CBR was 14.8 months.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sam Whiting, MD, PhD
Organizational Affiliation
Calithera Biosciences, Inc
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Brimingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of South Alabama, Mitchell Cancer Institute
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Georgetown University - Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Washington Cancer Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University Cancer and Blood Center
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Winship Cancer Institute - Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30332
Country
United States
Facility Name
Northwest Georgia Oncology
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Weinberg Cancer Institute at Franklin Square
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Saint Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
JTCC at Hackensack UMC
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Magee Womens Hospital - UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Charleston Hematology Oncology Associates
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414
Country
United States
Facility Name
Greenville Health System (GHS) Cancer Institute
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
West Cancer Center
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Northwest Medical Specialties, PLLC
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Froedtert and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.calithera.com
Description
Company Website

Learn more about this trial

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

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