Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mara Chambers
• Collaborator: Novartis
• Treatments: Aromatase Inhibitors; Estradiol; Everolimus; Fulvestrant; Sirolimus

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

• Adequate organ function defined as follows: Adequate renal function, defined by a serum creatinine within the upper limits of normal, Adequate liver function, defined by a bilirubin of < 1.5 the upper limit of normal (ULN) and aspartate aminotransferase (AST), alanine aminotransferase (ALT) of ≤ 2.5 times the ULN, Adequate bone marrow function, defined as an absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count (PLT) >100,000/ul, Hb >9 gm/dl, international normalized ratio (INR) <1.3, and because fulvestrant is administered intramuscularly, it should not be used in patients with bleeding diatheses, thrombocytopenia or in patients on anticoagulants

• Patients will be asked to provide a tumor paraffin block if available

• Ability to understand and sign a written informed consent for participation in the trial

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

• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the clinical trial

• Prior treatment with an mTOR inhibitor

• Treatment with a non-approved or investigational drug within 30 days or 5 half-lives of the drug, whichever is greater, before Day 1 of study treatment

• In the opinion of the investigator, bleeding diathesis or anticoagulation therapy that would preclude intramuscular injections

• History of hypersensitivity to castor oil