Exemestane in Combination With Fulvestrant in Postmenopausal Women With Hormone Sensitive Advanced Breast Cancer

Phase 2

Completed

Brief Summary: The purpose of this trial is to evaluate time to progression in women with hormone responsive advanced breast cancer treated with a combination of exemestane and fulvestrant.

Recruitment & Eligibility

Inclusion Criteria

Proven breast cancer
Metastatic or locally advanced breast cancer
Hormonally responsive disease defined as estrogen (ER) and/ or progesterone receptor (PR) positive (>10% staining by immunohistochemistry)
Postmenopausal status
No more than 1 prior chemotherapy for stage IV metastatic breast cancer allowed
ECOG (Eastern Cooperative Oncology Group) performance status 0-2
Adequate organ function

Exclusion Criteria

No prior Exemestane or Fulvestrant
Uncontrolled intercurrent illness including but not limited to:
- ongoing or active infection
- symptomatic congestive heart failure
- unstable angina pectoris
- cardiac arrhythmia
- myocardial infarction within the last 3 months
- psychiatric illness/social situations that would limit compliance with study
Lymphangitic pulmonary disease; carcinomatous meningitis, bone marrow only metastases; and a rising tumor marker without any other site of metastatic disease.
Presence of bleeding diathesis or coagulopathy, patients requiring coumadin

Arm && Interventions

Group	Intervention	Description
single-arm study	Fulvestrant	Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection
single-arm study	Exemestane	Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection

Primary Outcome Measures

Name	Time	Method
Time to Progression (TTP) in Women With Hormone Responsive Advanced Breast Cancer Treated With Combination of Exemestane and Fulvestrant.	Every 2 cycles up to 2 years	TTP is defined as the time from first treatment to objective evidence of progression on the basis of radiological evaluation and/or physical exam (if physical examination identifies a site of measurable disease). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures

Name	Time	Method
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease)	Every 2 cycles, up to 1 year	Response and progression was evaluated after every 2 cycles by physical examination and imaging studies using the international RECIST criteria. Complete Response (CR), Partial Response (PR), Overall Response Rate (ORR), Stable Disease (SD), Progressive Disease (PD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions; Overall Response Rate (ORR), CR+PR
Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant	Day 7 and Day 120	5 mL of venous whole blood was obtained before dosing and then at 1, 2, 4, 6, 8, and 24 hours after exemestane ingestion on each of the 2 time points.
Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels	Prestudy, Day 7 and Day 120