Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cabozantinib
Fulvestrant
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring ER+, PR+, Human Epidermal Growth Factor Receptor (HER) 2 negative, metastatic
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
Sites / Locations
- Beth Israel Deaconess Medical Center
- Dana Farber Cancer Institute
- Massachusetts General Hospital
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cabozantinib plus fulvestrant
Arm Description
Combination therapy with cabozantinib 60 mg daily plus fulvestrant 500 mg monthly Intramuscularly (IM)
Outcomes
Primary Outcome Measures
Bone Scan Response Rate
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
To evaluate overall response rate (ORR) (defined as the percentage of patients experiencing a complete response or partial response)
Overall Survival
To evaluate Overall Survival
Progression Free Survival
To evaluate Progression Free Survival
Full Information
NCT ID
NCT01441947
First Posted
September 22, 2011
Last Updated
January 7, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Exelixis
1. Study Identification
Unique Protocol Identification Number
NCT01441947
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2011 (undefined)
Primary Completion Date
December 2020 (Actual)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Exelixis
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
ER+, PR+, Human Epidermal Growth Factor Receptor (HER) 2 negative, metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cabozantinib plus fulvestrant
Arm Type
Experimental
Arm Description
Combination therapy with cabozantinib 60 mg daily plus fulvestrant 500 mg monthly Intramuscularly (IM)
Intervention Type
Drug
Intervention Name(s)
Cabozantinib
Other Intervention Name(s)
XL184
Intervention Description
Part of combination arm
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
Faslodex
Intervention Description
part of combination arm
Primary Outcome Measure Information:
Title
Bone Scan Response Rate
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
To evaluate overall response rate (ORR) (defined as the percentage of patients experiencing a complete response or partial response)
Time Frame
2 years
Title
Overall Survival
Description
To evaluate Overall Survival
Time Frame
2 years
Title
Progression Free Survival
Description
To evaluate Progression Free Survival
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven J Isakoff, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02214
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32463152
Citation
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.
Results Reference
derived
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Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer
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