Clinical trial NCT01658176: Study Of PF-04691502 (PI3K/mTOR Inhibitor) In Combination With Exemestane Compared With Exemestane Alone In Patients With Advanced Breast Cancer
Official title: An Open-Label Randomized Phase 2 Study Of PF-04691502 (PI3K/mTOR Inhibitor) In Combination With Exemestane Compared With Exemestane Alone In Patients With Estrogen Receptor Positive, Her-2 Negative Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Estrogen receptor positive
Her-2 negative
advanced breast cancer
Breast Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-08-06
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: PF-04691502 is an inhibitor of PI3K and mTOR kinase. Exemestane is an aromatase inhibitor for the treatment of advanced breast cancer in women whose disease has progressed following tamoxifen therapy. The combination of PF-04691502 and exemestane might mitigate resistance to hormonal therapy and result in greater clinical benefit than exemestane alone in women with estrogen receptor positive advanced breast cancer.


Eligibility criteria: Inclusion Criteria:

* Inoperable estrogen receptor positive, Her-2 negative advanced breast cancer
* Previously treated with an aromatase inhibitor
* Primary or secondary hormone resistance
* Acceptable glucose control, bone marrow, liver and kidney function

Exclusion Criteria:

* Inflammatory breast carcinoma
* Prior therapy with an agent active on PI3K, Akt, and/or mTOR
* Known hypersensitivity to exemestane
* Significant gastrointestinal abnormalities which may impair intake, transit, or absorption of the study drugs
* Current or anticipated need for food or drugs that are known inhibitors or inducers of CYP3A4

Primary outcomes:
measure: Progression-Free Survival
timeFrame: Baseline up to month 12
Secondary outcomes:
measure: Objective tumor response using RECIST
timeFrame: Baseline up to month 12
measure: Duration of tumor response
timeFrame: Baseline up to month 12
measure: Clinical benefit response
timeFrame: Baseline up to month 12
measure: Overall Survival
timeFrame: 2 years
measure: Biomarkers related to PI3K/mTOR signal deregulation and markers of cellular proliferation and apoptosis in primary tumor tissue
timeFrame: Baseline
measure: Maximum concentration (Cmax) of single dose of PF-04691502
timeFrame: Day 2 Pre-dose, and 1 , 2, 4 and 24 hours post-dose
measure: Maximum concentration (Cmax) of single dose exemestane
timeFrame: Day 1 pre-dose, and 1, 2, 4 and 24 hours post-dose
measure: Maximum concentration (Cmax) of PF-04691502 and exemestane when administered in combination
timeFrame: Day 8 Pre-dose, and 1, 2, 4 and 24 hours post-dose, Weel 5, 9, 13, 17, 21, and 25
measure: Pharmacodynamic endpoints including serum glucose, insulin, HbA1c, cholesterol and triglycerides
timeFrame: 12 months
measure: Heath related quality of life measured by Functional Assessment of Cancer Therapy- Breast
timeFrame: 12 months
measure: Area under the plasma concentration versus time curve (AUC) of single dose of PF-04691502
timeFrame: Day 2 Pre-dose, and 1 , 2, 4 and 24 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) of single dose exemestane
timeFrame: Day 1 pre-dose, and 1, 2, 4 and 24 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) of PF-04691502 and exemestane when administered in combination
timeFrame: Day 8 Pre-dose, and 1, 2, 4 and 24 hours post-dose, Weel 5, 9, 13, 17, 21, and 25
Other outcomes:
Locations:
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: