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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
Steven Isakoff, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01441947
First received: September 22, 2011
Last updated: November 10, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Cabozantinib
Drug: Fulvestrant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer With Involvement of Bone

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Bone Scan Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate overall response rate (ORR) (defined as the percentage of patients experiencing a complete response or partial response)

  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate Overall Survival

  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate Progression Free Survival

  • Effects on bone and tumor markers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the effects of cabozantinib on biochemical markers of bone turnover and tumor markers

  • Skeletal related event rates (includes analgesic usage, incidence of fractures, need for radiation or surgical intervention and pain at sites of bone disease) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    All intercurrent adverse events, treatments and interventions will be recorded. For the purpose of determining the effects of cabozantinib treatment on pain and analgesic medication usage, pain will be assessed by a participant-reported questionnaire, and daily analgesic medication usage will be recorded during regular intervals.

  • FDG-PET (Flurodeoxyglucose Positron Emission Tomography) Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate FDG-PET response rate


Estimated Enrollment: 50
Study Start Date: October 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cabozantinib plus fulvestrant
Combination therapy with cabozantinib 60 mg daily plus fulvestrant 500 mg monthly IM
Drug: Cabozantinib
Part of combination arm
Other Name: XL184
Drug: Fulvestrant
part of combination arm
Other Name: Faslodex

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 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 HER2 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 FXa 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441947

Contacts
Contact: Steven J Isakoff, MD, PhD 617-726-4920 sisakoff@partners.org

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States
Contact: Steven Come       scome@bidmc.harvard.edu   
Principal Investigator: Steve Come, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States
Contact: Sara Tolaney       sara_tolaney@dfci.harvard.edu   
Principal Investigator: Sara Tolaney, MD MPH         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
Contact: Steve Isakoff, MD PhD    617-726-4920    sjisakoff@partners.org   
United States, New York
Memorial Sloan Kettering Cancer Center Active, not recruiting
New York, New York, United States, 10065
Sponsors and Collaborators
Massachusetts General Hospital
Exelixis
Investigators
Principal Investigator: Steven J Isakoff, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Steven Isakoff, MD, PhD, Principal Investigator, Attending Physician in Medical Oncology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01441947     History of Changes
Other Study ID Numbers: 11-208
Study First Received: September 22, 2011
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
ER+
PR+
HER2-
metastatic

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Fulvestrant
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014