Clinical trial NCT01738438: Cabozantinib for Metastatic Triple Negative BrCa
Official title: A Phase II Study of XL184 (Cabozantinib) for Metastatic Triple-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Metastatic
Triple Negative
Stage IV
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2012-11-30
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: 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 outcomes:
measure: Progression Free Survival
timeFrame: 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).
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute at Faulkner Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Sara Tolaney, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.