Clinical trial NCT01441947: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: ER+
PR+
Human Epidermal Growth Factor Receptor (HER) 2 negative
metastatic
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Exelixis
First posted: 2011-09-28
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Bone Scan Response Rate
timeFrame: 2 years
Secondary outcomes:
measure: Overall Response Rate by RECIST v 1.1
timeFrame: 2 years
measure: Overall Survival
timeFrame: 5 years
measure: Progression Free Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Isakoff, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.