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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Cabozantinib; Drug: Fulvestrant

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cabozantinib; Oral cabozantinib therapy daily	Drug: Cabozantinib; Given orally daily with a starting dose of 40 mg; Other Names: XL184
Experimental: Cabozantinib plus fulvestrant; Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM)	Drug: Cabozantinib; Given orally daily with a starting dose of 40 mg; Other Names: XL184; 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; Other Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Scan Response Rate	Bone scan response rate will be defined as the percentage of patients experiencing a complete resolution of bone lesions or partial response in the isotope bone scan per Bone Scan Time Point Response Criteria, as defined in the protocol. Complete resolution is defined as the disappearance of all areas of radiotracer uptake attributable to metastatic disease, and a partial response is defined as significant improvement in radiotracer uptake in areas attributable to metastatic disease, but not meeting the criteria for CR.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate by RECIST v 1.1	The overall response rate (ORR) is defined as the percentage of patients experiencing a complete response or partial response on PET imaging per mRECIST (modified response evaluation criteria in solid tumors), as defined in the protocol. A complete response is defined as resolution of all areas of FDG uptake attributable to metastatic disease. A partial response is defined as significantly decreased FDG uptake in areas attributable to metastatic disease, but not meeting the criteria for a complete response.	2 years
Overall Survival	Overall Survival (OS) is defined as the difference between the date of a patient's enrollment onto this study until the date of death. Patients who are alive at last contact will be censored for OS at this date.	5 years
Progression Free Survival	Progression Free Survival (PFS) is defined as the difference between the date of a patient's enrollment onto this study until the earlier of the date of progression or the date of death. Patients who are alive and progression-free at last contact will be censored for PFS at this date.	5 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Exelixis
• Investigators: Principal Investigator: Steven J Isakoff, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): December 12, 2016
• Study Completion (Actual): August 9, 2019

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimated): September 28, 2011

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: metastatic; ER+; PR+; Human Epidermal Growth Factor Receptor (HER) 2 negative
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Fulvestrant
• Other Study ID Numbers: 11-208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes