Cabozantinib for Metastatic Triple Negative BrCa

NCT ID: NCT01738438

Last Updated: 2016-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-05-31

Brief Summary

In this research study, we are looking at the anti-tumor effects of Cabozantinib (XL184) in metastatic breast cancer. Data suggest that MET expression and activation are important for initiation and progression of triple-negative breast cancer (TNBC). We evaluated the efficacy of cabozantinib (XL184), a novel inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2, in patients with metastatic TNBC.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the activity of cabozantinib, as defined by objective response rate in patients with triple-negative metastatic breast cancer

Secondary

• To evaluate progression free survival
• To evaluate c-Met and phospho c-Met expression in archival tumor tissue
• To evaluate the incidence of c-Met amplified circulating tumor cells at baseline
• To evaluate potential plasma biomarkers of cabozantinib

DESIGN:

This study uses a two-stage design enrolling 35 patients to evaluate efficacy of cabozantinib based on overall response defined as complete or partial response per RECIST1.1 criteria. The null and alternative overall response rates were 5% and 20%. If one or more patients enrolled in the stage one cohort (n=13 patients) achieve PR or better then accrual proceeds to stage two (n=22 patients).

Conditions

Breast Cancer

Keywords

Metastatic; Triple Negative; Stage IV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabozantinib

Cabozantinib was given at a dose of 60 mg orally once per day for 21 day cycles. Treatment continued in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Interventions

Cabozantinib

Intervention Type: DRUG

Other Intervention Names

XL184

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed invasive breast cancer with stage IV disease
• Primary tumor and/or metastasis must be ER-negative, PR-negative and HER2-negative
• May have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer. Must be off treatment for at least 21 days prior to enrollment
• Must have discontinued all biologic therapy at least 14 days before enrollment
• May have received prior radiation therapy in the early stage or metastatic setting, but must have completed treatment at least 14 days prior to enrollment
• Must agree to use medically acceptable methods of contraception
• Confirmed availability of formalin-fixed, paraffin-embedded tumor tissue
• Able to swallow tablets

Exclusion Criteria

• Pregnant or breastfeeding
• Received another investigational agent within 14 days prior to enrollment
• Received prior c-Met inhibitor
• Known brain metastases that are untreated, symptomatic or require therapy to control symptoms
• Psychiatric illness or social situation that could limit ability to comply with study requirements
• Require concomitant treatment in therapeutic doses with anticoagulants or antiplatelet agents
• Diagnosis of another malignancy requiring systemic treatment within the last two years (except non-melanoma skin cancer or in-situ carcinoma of the cervix)
• Known to be positive for HIV
• Active infection requiring IV antibiotics at Day 1 of cycle 1
• Uncontrolled, significant intercurrent illness
• Requires chronic concomitant treatment of a strong CYP3A4 inducer
• tumor in contact with, invading or encasing major blood vessels
• Have experienced clinically significant gastrointestinal bleeding within 6 months, hemoptysis of more than 0.5 teaspoon of red blood within 3 months or other signs indicative of pulmonary hemorrhage within 3 months of enrollment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Sara Tolaney

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sara Tolaney, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute at Faulkner Hospital

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Weber ZT, Collier KA, Tallman D, Forman J, Shukla S, Asad S, Rhoades J, Freeman S, Parsons HA, Williams NO, Barroso-Sousa R, Stover EH, Mahdi H, Cibulskis C, Lennon NJ, Ha G, Adalsteinsson VA, Tolaney SM, Stover DG. Modeling clonal structure over narrow time frames via circulating tumor DNA in metastatic breast cancer. Genome Med. 2021 May 20;13(1):89. doi: 10.1186/s13073-021-00895-x.

Reference Type: DERIVED

PMID: 34016182 (View on PubMed)

Other Identifiers

12-431

Identifier Type: -

Identifier Source: org_study_id