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

NCT01441947 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 11-208
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Cancer

Keywords

ER+; PR+; Human Epidermal Growth Factor Receptor (HER) 2 negative; metastatic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Response Rate by RECIST v 1.1

  2 years

• Overall Survival

  5 years

• Progression Free Survival

  5 years

Study Arms (2)

Cabozantinib

EXPERIMENTAL

Oral cabozantinib therapy daily

Drug: Cabozantinib

Cabozantinib plus fulvestrant

EXPERIMENTAL

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

Drug: Cabozantinib; Drug: Fulvestrant

Interventions

Cabozantinib DRUG

Given orally daily with a starting dose of 40 mg

Also known as: XL184

Cabozantinib; Cabozantinib plus fulvestrant

Fulvestrant DRUG

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

Also known as: Faslodex

Cabozantinib plus fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Exelixis: collaborator

Study Sites (4)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 32463152 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

cabozantinib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Primary (bone scan response rate) and reported secondary (ORR, OS, PFS) objectives are only applicable for the main cohort (Cabozantinib only), and objectives for the pilot cohort are listed separately. Per protocol section 14, "all secondary endpoint analyses of this trial are considered exploratory." We reported the secondary objectives for the main cohort listed above despite these being considered exploratory, as they were readily available. The remaining exploratory analyses were not done.

Results Point of Contact

• Title: Steven Isakoff, MD, PhD
• Organization: Massachusetts General Hospital

sisakoff@partners.org

617-643-5415

Study Officials

• Steven J Isakoff, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Attending Physician in Medical Oncology

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: September 28, 2011
• Study Start: October 1, 2011
• Primary Completion: December 12, 2016
• Study Completion: August 9, 2019
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)