Cabozantinib for Metastatic Triple Negative BrCa

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01738438
First received: November 28, 2012
Last updated: July 18, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Breast Cancer
Drug: Cabozantinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of XL184 (Cabozantinib) for Metastatic Triple-Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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:
  • Progression Free Survival [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: February 2013
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: XL184

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).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738438

Locations
United States, Massachusetts
Dana-Farber Cancer Institute at Faulkner Hospital
Boston, Massachusetts, United States, 02130
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Sara Tolaney, MD, MPH Dana-Farber Cancer Institute
  More Information

Responsible Party: Sara Tolaney, Prinicipal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01738438     History of Changes
Other Study ID Numbers: 12-431 
Study First Received: November 28, 2012
Results First Received: May 27, 2016
Last Updated: July 18, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Dana-Farber Cancer Institute:
Metastatic
Triple Negative
Stage IV

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 23, 2016