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

Sponsor

Calithera Biosciences, Inc (Industry)

Overall Status

Completed

CT.gov ID

NCT03057600

Collaborator

(none)

Enrollment

Locations

Arms

30.4

Actual Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CX-839-007 is an open-label Phase 2 study of the combination of CB-839 with paclitaxel in patients 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.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer TNBC - Triple-Negative Breast Cancer	Drug: Paclitaxel Drug: CB-839	Phase 2

Detailed Description

CX-839-007 is an open-label Phase 2 study of the combination of CB-839 with paclitaxel in patients of African ancestry and non-African ancestry with advanced triple negative breast cancer. Multiple single-arm cohorts will be enrolled in which 800 mg BID CB-839 will be administered in combination with the full approved dose of paclitaxel.

Patients 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

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients 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 ancestryPatients 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 15, 2017

Actual Primary Completion Date :

Nov 25, 2019

Actual Study Completion Date :

Nov 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 - African ancestry, 3rd line+ Intervention = Pac-CB combination Patients must self-identify as African ancestry (AA; 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.	Drug: Paclitaxel standard weekly paclitaxel in 28-day cycles Other Names: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID) Other Names: telaglenastat
Experimental: Cohort 2 - African ancestry, 1st line Intervention = Pac-CB combination Patients 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.	Drug: Paclitaxel standard weekly paclitaxel in 28-day cycles Other Names: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID) Other Names: telaglenastat
Experimental: Cohort 3 - Non-AA, 3rd line+ Intervention = Pac-CB combination Patients do not self-identify as African ancestry. Otherwise have the same criteria as Cohort 1.	Drug: Paclitaxel standard weekly paclitaxel in 28-day cycles Other Names: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID) Other Names: telaglenastat
Experimental: Cohort 4 - Non-AA, 1st line Intervention = Pac-CB combination Patients do not self-identify as African ancestry. Otherwise have the same criteria as Cohort 2.	Drug: Paclitaxel standard weekly paclitaxel in 28-day cycles Other Names: Taxane Drug: CB-839 CB-839 administered as oral tablets twice daily (BID) Other Names: telaglenastat

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [Approximately 15 months]]

Secondary Outcome Measures

Progression free survival (PFS) [Approximately 18 months]
Overall survival (OS) [Up to 36 months]
Duration of response (DOR) [Up to 18 months]
Clinical benefit rate (CBR) [Approximately 18 months]

Other Outcome Measures

Type, incidence, severity, seriousness, and relatedness of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 [Approximately 15 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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%) and human epidermal growth factor receptor 2 (HER2) negative (fluorescent in situ hybridization [FISH] negative or immunohistochemistry (IHC) 0-1+)

, progesterone receptor (PR), and .

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 CTCAE ver.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 C1D1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Brimingham	Birmingham	Alabama	United States	35294
2	University of South Alabama, Mitchell Cancer Institute	Mobile	Alabama	United States	36604
3	Yale Cancer Center	New Haven	Connecticut	United States	06511
4	Georgetown University - Lombardi Comprehensive Cancer Center	Washington	District of Columbia	United States	20007
5	Washington Cancer Institute	Washington	District of Columbia	United States	20010
6	University of Miami	Miami	Florida	United States	33176
7	Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
8	University Cancer and Blood Center	Athens	Georgia	United States	30607
9	Winship Cancer Institute - Emory University	Atlanta	Georgia	United States	30332
10	Northwest Georgia Oncology	Marietta	Georgia	United States	30060
11	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
12	Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland	United States	21237
13	Henry Ford Hospital	Detroit	Michigan	United States	48202
14	Saint Louis University	Saint Louis	Missouri	United States	63110
15	JTCC at Hackensack UMC	Hackensack	New Jersey	United States	07601
16	Columbia University	New York	New York	United States	10032
17	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
18	Magee Womens Hospital - UPMC	Pittsburgh	Pennsylvania	United States	15213
19	Charleston Hematology Oncology Associates	Charleston	South Carolina	United States	29414
20	Greenville Health System (GHS) Cancer Institute	Greenville	South Carolina	United States	29605
21	West Cancer Center	Germantown	Tennessee	United States	38138
22	Baylor College of Medicine	Houston	Texas	United States	77030
23	MD Anderson	Houston	Texas	United States	77030
24	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
25	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226