A Phase II Study of Combined Fulvestrant (Faslodex) and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure
Overview
- Phase
- Phase 2
- Intervention
- Everolimus
- Conditions
- Breast Cancer
- Sponsor
- Mara Chambers
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Time to Progression
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary objective of this study is to determine if estrogen receptor-targeted therapy with fulvestrant used in combination with Everolimus is an effective and safe therapy for women with hormone receptor positive metastatic breast cancer after failure of aromatase inhibitor therapy.
Detailed Description
Fulvestrant, which degrades ER, is used after aromatase inhibitor (AI) failure in metastatic breast cancer but resistance develops quickly. We hypothesized that using everolimus to inhibit mammalian target of rapamycin (mTOR), a key signaling pathway in endocrine resistance, may delay fulvestrant resistance in patients and thus improve its efficacy. We conducted a phase II trial of combined fulvestrant and everolimus in postmenopausal women with disease progression or relapse after an AI. Primary endpoint was time to progression (TTP) and secondary endpoints included objective response rate, clinical benefit rate (CBR), safety, and biomarker correlates. Tumor blocks were collected and biopsy of accessible tumor was done for future biomarker analysis.
Investigators
Mara Chambers
Sponsor-Investigator
University of Kentucky
Eligibility Criteria
Inclusion Criteria
- •Postmenopausal status, defined as any one of the following criteria: Documented history of bilateral oophorectomy, Age 60 years or more, OR Age 45 to 59 and satisfying one or more of the following criteria: Amenorrhea for at least 12 months and intact uterus OR Amenorrhea for less than 12 months and a follicle stimulating hormone (FSH) concentration - within postmenopausal range including: Patients who have had a hysterectomy or Patients who have received hormone replacement
- •Patients must have histologically confirmed invasive breast cancer
- •Metastatic or locally advanced disease
- •Patients must have estrogen receptor and/or progesterone receptor positive disease
- •Measurable or evaluable disease
- •Failure of aromatase inhibitor therapy within the previous 6 months. Patients who received prior tamoxifen are eligible to enroll
- •Prior aromatase inhibitor therapy or other endocrine therapy must be discontinued at least 1 week prior to enrollment and any toxicity from such therapy must have reverted to grade I or less at the time of enrollment
- •Patients must not have received chemotherapy, radiation therapy, or had surgery within 4 weeks prior to enrollment and any toxicity from such therapy must have recovered to grade 1 or less prior to enrollment
- •Patients must not have received either of the study medications previously
- •WHO performance status of 0, 1, or 2
Exclusion Criteria
- •Known severe hypersensitivity to everolimus (or similar drugs) or any of the excipients of this product
- •Premenopausal status
- •Other coexisting malignancies with the exception of basal cell carcinoma or cervical cancer in situ
- •Patients with brain metastasis or leptomeningeal involvement
- •Patients with malignant pleural effusion or ascites only disease
- •Rapidly progressive visceral disease
- •WHO performance status of 3 or 4
- •As judged by the investigator, uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection, Symptomatic congestive heart failure, Unstable angina pectoris or significant cardiac arrhythmia, Psychiatric illness/social situations that would limit compliance with study requirements, Severely impaired lung function such as severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease, a known forced expiratory volume at one second (FEV1) of \< 1.5 liters, or dyspnea of grade III or greater, Uncontrolled diabetes as defined by a fasting blood sugar (FBS) of \> 1.5 ULM, Known liver disease such as cirrhosis or chronic hepatitis, Known HIV positivity, OR known condition causing malabsorption
- •Chronic treatment with systemic steroids or other immunosuppressive agents
- •Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
Arms & Interventions
Fulvestrant + Everolimus
Fulvestrant + Everolimus Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
Intervention: Everolimus
Fulvestrant + Everolimus
Fulvestrant + Everolimus Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that.
Intervention: Fulvestrant
Outcomes
Primary Outcomes
Time to Progression
Time Frame: Duration of time start of treatment to time of documented progression or death
Secondary Outcomes
- Objective Response Rates(Evaluated 60 days after therapy start)
- Clinical Benefit Rate(Duration of response or stable disease for 24 weeks or more)