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

Sponsor

Pfizer (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01658176

Collaborator

(none)

Enrollment

Arms

26.9

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: PF-04691502 Drug: Exemestane Drug: Exemestane	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2013

Anticipated Primary Completion Date :

Apr 1, 2015

Anticipated Study Completion Date :

Apr 1, 2015

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: PF-04691502 + Exemestane

PF-04691502 in combination with Exemestane

Drug: PF-04691502

PF-04691502 administered orally at 8 mg as a continuous daily dosing schedule

Drug: Exemestane

Exemestane administered orally at 25 mg as a continuous daily dosing schedule

Active Comparator: Exemestane

Exemestane alone

Drug: Exemestane

Exemestane administered orally at 25 mg as a continuous daily dosing schedule

Outcome Measures

Primary Outcome Measures

Progression-Free Survival [Baseline up to month 12]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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