Study Of PF-04691502 (PI3K/mTOR Inhibitor) In Combination With Exemestane Compared With Exemestane Alone In Patients With Advanced Breast Cancer

Study Overview
=================
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.

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

Conditions
-----------------
Breast Neoplasms

Intervention / Treatment
-----------------
* Drug: PF-04691502
* Drug: Exemestane
* Drug: Exemestane


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04691502 + Exemestane<br>PF-04691502 in combination with Exemestane | Drug: PF-04691502<br>* PF-04691502 administered orally at 8 mg as a continuous daily dosing schedule<br>Drug: Exemestane<br>* Exemestane administered orally at 25 mg as a continuous daily dosing schedule<br>|
| Active Comparator: Exemestane<br>Exemestane alone | Drug: Exemestane<br>* Exemestane administered orally at 25 mg as a continuous daily dosing schedule<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival |  | Baseline up to month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response using RECIST |  | Baseline up to month 12 | 
| Duration of tumor response |  | Baseline up to month 12 | 
| Clinical benefit response |  | Baseline up to month 12 | 
| Overall Survival |  | 2 years | 
| Biomarkers related to PI3K/mTOR signal deregulation and markers of cellular proliferation and apoptosis in primary tumor tissue |  | Baseline | 
| Maximum concentration (Cmax) of single dose of PF-04691502 |  | Day 2 Pre-dose, and 1 , 2, 4 and 24 hours post-dose | 
| Maximum concentration (Cmax) of single dose exemestane |  | Day 1 pre-dose, and 1, 2, 4 and 24 hours post-dose | 
| Maximum concentration (Cmax) of PF-04691502 and exemestane when administered in combination |  | Day 8 Pre-dose, and 1, 2, 4 and 24 hours post-dose, Weel 5, 9, 13, 17, 21, and 25 | 
| Pharmacodynamic endpoints including serum glucose, insulin, HbA1c, cholesterol and triglycerides |  | 12 months | 
| Heath related quality of life measured by Functional Assessment of Cancer Therapy- Breast |  | 12 months | 
| Area under the plasma concentration versus time curve (AUC) of single dose of PF-04691502 |  | Day 2 Pre-dose, and 1 , 2, 4 and 24 hours post-dose | 
| Area under the plasma concentration versus time curve (AUC) of single dose exemestane |  | Day 1 pre-dose, and 1, 2, 4 and 24 hours post-dose | 
| Area under the plasma concentration versus time curve (AUC) of PF-04691502 and exemestane when administered in combination |  | Day 8 Pre-dose, and 1, 2, 4 and 24 hours post-dose, Weel 5, 9, 13, 17, 21, and 25 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Estrogen receptor positive, Her-2 negative, advanced breast cancer, Breast Cancer