Breast Cancer
Conditions
Keywords
ER+, PR+, Human Epidermal Growth Factor Receptor (HER) 2 negative, metastatic
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.
Interventions
DRUGCabozantinib
Given orally daily with a starting dose of 40 mg
DRUGFulvestrant
Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after
Sponsors
Exelixis
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Scan Response Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate by RECIST v 1.1 | 2 years | 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. |
| Overall Survival | 5 years | 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. |
| Progression Free Survival | 5 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cabozantinib Oral cabozantinib therapy daily
Cabozantinib: Given orally daily with a starting dose of 40 mg | 55 |
| Cabozantinib Plus Fulvestrant Combination therapy with oral cabozantinib daily plus fulvestrant monthly Intramuscularly (IM)
Cabozantinib: Given orally daily with a starting dose of 40 mg
Fulvestrant: Given intramuscularly 500 mg on Days 1 and 15 of the first 28 day cycle, then on Day 1 only each cycle after | 13 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Cabozantinib Plus Fulvestrant | Cabozantinib |
|---|---|---|---|
| Age, Continuous | 56 years | 63 years | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 12 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) White | 57 Participants | 12 Participants | 45 Participants |
| Sex: Female, Male Female | 68 Participants | 13 Participants | 55 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 52 | 12 / 13 |
| other Total, other adverse events | 51 / 52 | 13 / 13 |
| serious Total, serious adverse events | 13 / 52 | 3 / 13 |
Outcome results
Primary
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.
Time frame: 2 years
Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.1, only patients in the main cabozantinib cohort were included in the primary analysis. There are no primary endpoints for the pilot cabozantinib/ fulvestrant cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabozantinib | Bone Scan Response Rate | 38.5 percentage of participants |
Secondary
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.
Time frame: 2 years
Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.4, ORR is a secondary endpoint only for the main cabozantinib cohort; endpoints for the pilot cohort are listed separately. Additionally, per protocol section 14.4, All secondary endpoint analyses of this trial are considered exploratory. Results for ORR are available, so we are reporting them here even though this endpoint was considered exploratory.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cabozantinib | Overall Response Rate by RECIST v 1.1 | 0 Participants |
Secondary
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.
Time frame: 5 years
Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.4, OS is a secondary endpoint only for the main cabozantinib cohort; endpoints for the pilot cohort are listed separately. Additionally, per protocol section 14.4, All secondary endpoint analyses of this trial are considered exploratory. Results for OS are available, so we are reporting them here even though this endpoint was considered exploratory.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib | Overall Survival | 19.6 months |
Secondary
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.
Time frame: 5 years
Population: 55 patients initially enrolled to the Cabozantinib cohort, but 3 withdrew prior to starting study treatment. Per protocol section 14.4, PFS is a secondary endpoint only for the main cabozantinib cohort; endpoints for the pilot cohort are listed separately. Additionally, per protocol section 14.4, All secondary endpoint analyses of this trial are considered exploratory. Results for PFS are available, so we are reporting them here even though this endpoint was considered exploratory.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib | Progression Free Survival | 4.3 units on a scale |