Cabozantinib for Metastatic Triple Negative BrCa

A Phase II Study of XL184 (Cabozantinib) for Metastatic Triple-Negative Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Cabozantinib

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).

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02130
      • Dana-Farber Cancer Institute at Faulkner Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Cabozantinib; Other Names: XL184

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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.	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).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	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.	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).

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: November 28, 2012
• First Submitted That Met QC Criteria: November 29, 2012
• First Posted (Estimate): November 30, 2012

Study Record Updates

• Last Update Posted (Estimate): December 6, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Metastatic; Triple Negative; Stage IV
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 12-431

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO