Cabozantinib for Metastatic Triple Negative BrCa

Phase 2

Completed

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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Cabozantinib	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).	The objective response rate (ORR) was defined as achieving complete response (CR) or partial response (PR) on treatment based on RECIST1.1 criteria. For target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Confirmatory scans were required 3 weeks following initial documentation.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	Disease was evaluated radiologically at baseline, week 6 and every 9 weeks on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-17).	Progression-free survival (PFS) estimated using Kaplan-Meier methods was defined as the time from registration to documented disease progression (PD) or death. Based on RECIST1.1, radiographic PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning therapy, the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Patients who were event-free were censored at the date of their last disease evaluation.

Locations (3): Dana-Farber Cancer Institute at Faulkner Hospital
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Boston, Massachusetts, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States