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

November 28, 2012
July 18, 2016
February 2013
May 2015   (final data collection date for primary outcome measure)
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.
Evaluation of XL184 based on objective response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To evaluate the activity of XL184, as defined by objective response rate (ORR) in patients with triple-negative metastatic breast cancer
Complete list of historical versions of study NCT01738438 on ClinicalTrials.gov Archive Site
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.
  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluation of Progression Free Survival
  • c-Met and phospho c-Met expression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate c-Met and phospho c-Met expression in archival tumor tissue
  • Incidence of c-Met amplified circulating tumor cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the incidence of c-Met amplified circulating tumor cells at baseline
  • Evaluation of potential serum biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate potential serum biomarkers of XL184
  • Evaluate PTEN loss and PI3K mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate PTEN loss and PI3K mutations in archival tumor tissue
  • Evaluate change in radiotracer uptake within tumor site [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate if the percent change in radiotracer uptake within the tumor site(s) from baseline to the first and second follow-up FDG-PET/CT correlates RECIST response
Not Provided
Not Provided
 
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.

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).

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
Drug: Cabozantinib
Other Name: XL184
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.
Intervention: Drug: Cabozantinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
May 2015
May 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01738438
12-431
Yes
No
Not Provided
Sara Tolaney, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
Not Provided
Principal Investigator: Sara Tolaney, MD, MPH Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP