Breast CancerPhase 2NCT01441947
Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer
A Phase 2 study testing Cabozantinib and Fulvestrant in people with Breast Cancer, run by Massachusetts General Hospital at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Cabozantinib and Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2011to 9 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02214
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Cabozantinib, Fulvestrant
- Keywords
- ER+, PR+, Human Epidermal Growth Factor Receptor (HER) 2 negative, metastatic
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL184
Given orally daily with a starting dose of 40 mg
FulvestrantDrug
Also called Faslodex
Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | Oral cabozantinib therapy daily Receives: Drug: Cabozantinib |
| Cabozantinib plus fulvestrant | Experimental | Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) Receives: Drug: Cabozantinib; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2011 (estimated)
- Study startOct 2011
- Primary completion12 Dec 2016
- Study completion9 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis
- Responsible party
- Principal investigator, Steven J Isakoff, MD, PhD, Massachusetts General Hospital
- Investigators
- Steven J Isakoff, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01441947
- Sponsor's protocol ID
- 11-208
- Status last verified
- May 2025
- First submitted
- 22 Sep 2011
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No
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.
PubMed 32463152
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Cabozantinib in Women With Metastatic Hormone-Receptor-Positive Breast Cancer With Involvement of Bone
- ClinicalTrials.gov ID
- NCT01441947
- Acronym / sponsor ID
- 11-208
- Conditions
- Breast Cancer
- Keywords
- ER+, PR+, Human Epidermal Growth Factor Receptor (HER) 2 negative, metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Exelixis
- Study start
- Oct 2011 (actual)
- Primary completion
- 12 Dec 2016 (actual)
- Study completion
- 9 Aug 2019 (actual)
- First posted
- 28 Sep 2011 (estimated)
- Results
- Posted 25 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cabozantinib | Experimental | Drug: CabozantinibOral cabozantinib therapy daily |
| Cabozantinib plus fulvestrant | Experimental | Drug: Cabozantinib, Drug: FulvestrantCombination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabozantinibAlso: XL184Given orally daily with a starting dose of 40 mg | Drug | Cabozantinib, Cabozantinib plus fulvestrant |
| FulvestrantAlso: FaslodexGiven intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after | Drug | Cabozantinib plus fulvestrant |
Primary outcome
Bone Scan Response Rate
Time frame: 2 years
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.
3 secondary outcomes
Overall Response Rate by RECIST v 1.1
Time frame: 2 years
Overall Survival
Time frame: 5 years
Progression Free Survival
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32463152Xu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven J Isakoff, MD, PhD principal investigator
Massachusetts General Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib and Fulvestrant in people with Breast Cancer, run by Massachusetts General Hospital at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Scan Response Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01441947, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.