Clinical Trials /

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

NCT01441947

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 11-208
  • NCT ID: NCT01441947

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
CabozantinibXL184Cabozantinib plus fulvestrant
FulvestrantFaslodexCabozantinib plus fulvestrant

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cabozantinib plus fulvestrantExperimentalCombination therapy with cabozantinib 60 mg daily plus fulvestrant 500 mg monthly Intramuscularly (IM)
  • Cabozantinib
  • Fulvestrant

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Bone Scan Response Rate
Time Frame:2 years
Safety Issue:
Description: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

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:To evaluate overall response rate (ORR) (defined as the percentage of patients experiencing a complete response or partial response)
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:To evaluate Overall Survival
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:To evaluate Progression Free Survival
Measure:Effects on bone and tumor markers
Time Frame:2 years
Safety Issue:
Description:To evaluate the effects of cabozantinib on biochemical markers of bone turnover and tumor markers
Measure: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
Safety Issue:
Description: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.
Measure:Fluorodeoxyglucose Positron Emission Tomography(FDG-PET) Response Rate
Time Frame:2 years
Safety Issue:
Description:To evaluate FDG-PET response rate

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

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

Last Updated

July 25, 2017