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

NCT ID: NCT01441947

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2019-08-09

Brief Summary

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

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cabozantinib

Oral cabozantinib therapy daily

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Given orally daily with a starting dose of 40 mg

Cabozantinib plus fulvestrant

Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM)

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Given orally daily with a starting dose of 40 mg

Fulvestrant

Intervention Type: DRUG

Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after

Interventions

Cabozantinib

Given orally daily with a starting dose of 40 mg

Intervention Type: DRUG

Fulvestrant

Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after

Intervention Type: DRUG

Other Intervention Names

XL184; Faslodex

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Steven J Isakoff, MD, PhD

Principal Investigator, Attending Physician in Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven J Isakoff, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Xu J, Higgins MJ, Tolaney SM, Come SE, Smith MR, Fornier M, Mahmood U, Baselga J, Yeap BY, Chabner BA, Isakoff SJ. A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases. Oncologist. 2020 Aug;25(8):652-660. doi: 10.1634/theoncologist.2020-0127. Epub 2020 Jun 18.

Reference Type: DERIVED

PMID: 32463152 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

11-208

Identifier Type: -

Identifier Source: org_study_id