Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer

Study Overview
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Brief Summary
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The study drug cabozantinib works by inhibiting several different proteins which are believed to be involved in breast cancer tumor growth, its ability to spread, and its ability to form new blood vessels. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to prevent cancer growth. The single agent portion of this study is now closed to accrual. This research study is now examining the efficacy of cabozantinib in combination with fulvestrant for treatment of hormone-receptor-positive breast cancer that has spread to bone.

Detailed Description
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Cabozantinib will be taken orally once a day in cycles of 28 days (4 weeks). Fulvestrant will be given intramuscularly on days 1 and 15 of cycle 1 and on day 1 of all subsequent cycles. On Day 1 of each cycle subjects will have the following tests and procedures: Performance status Physical exam Vital signs Routine blood samples Blood and urine samples to look at bone markers (Cycle 1 through 6 only) Subjects will also have the following additional tests and procedures: Tumor assessment by Computed Tomography (CT) scan and bone scan at Cycle 3, then every 12 weeks Blood or urine pregnancy test (if applicable) on Day 1 of Cycles 1, 2, 4, then every 12 weeks Urine sample and blood test for thyroid function (Cycle 1, 3, 5, then every 6 weeks) Blood test for breast cancer tumor marker (Cycle 1 and 4, then every 6 weeks) Pain questionnaire and painkiller medication diary at 7-day intervals during Week 3, Week 6, and every 6 weeks thereafter.

Official Title
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A Phase II Trial of Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer With Involvement of Bone

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Cabozantinib
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clear evidence of metastases to bone on isotope bone scan Histologically or cytologically confirmed metastatic Estrogen-receptor-positive (ER+) and/or Progesterone-receptor-positive (PR+) and Human Epidermal Growth Factor Receptor (HER) 2 negative breast cancer Received at least one prior line of hormonal or chemo-therapy for metastatic disease must be post menopausal Recovered from toxicities related to prior treatment, except alopecia, lymphopenia, or other non-clinically significant Adverse Events (AEs) Life expectancy > 3 months Adequate organ and marrow function Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception Able to lie flat for up to 45 minutes for imaging studies Able to swallow capsules or tablets Exclusion Criteria: Pregnant or breast-feeding Has experienced clinically-significant hematemesis or hemoptysis of > 0.5 teaspoons of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment Untreated, symptomatic or uncontrolled brain metastasis requiring current treatment including steroids and anti-convulsants more than 1 prior line of chemotherapy for treatment of metastatic breast cancer prior treatment with fulvestrant Requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or coumadin-related agents, thrombin or Factor Xa inhibitors, and antiplatelet agents (eg, clopidogrel) Uncontrolled or significant intercurrent illness Gastrointestinal disorders, particularly those associated with a high risk of perforation or fistula formation Active infection requiring systemic treatment Serious non-healing wound/ulcer/bone fracture History of organ transplant Concurrent uncompensated hypothyroidism or thyroid dysfunction Previously-identified allergy or hypersensitivity to components of the study treatment formulation Diagnosis of another malignancy, requiring systemic treatment, within the last 2 years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib plus fulvestrant<br>Combination therapy with cabozantinib 60 mg daily plus fulvestrant 500 mg monthly Intramuscularly (IM) | Drug: Cabozantinib<br>* Part of combination arm<br>* Other names: XL184;Drug: Fulvestrant<br>* part of combination arm<br>* Other names: Faslodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Scan Response Rate | To evaluate the bone scan response rate in patients with hormone-receptor-positive breast cancer with bone metastases receiving cabozantinib. Bone scan response rate will be defined as the percentage of patients experiencing a complete resolution or significant improvement in the bone scan. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To evaluate overall response rate (ORR) (defined as the percentage of patients experiencing a complete response or partial response) | 2 years | 
| Overall Survival | To evaluate Overall Survival | 2 years | 
| Progression Free Survival | To evaluate Progression Free Survival | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ER+, PR+, Human Epidermal Growth Factor Receptor (HER) 2 negative, metastatic