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

Phase 2

Withdrawn

• Conditions: Breast Neoplasms
• Interventions: Drug: PF-04691502; Drug: Exemestane

• Registration Number: NCT01658176
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-16
• Study First Submitted QC: 2012-08-01
• Study First Posted: 2012-08-06
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-26
• Last Update Posted: 2012-10-29
• Study Start: 2013-01
• Primary Completion: 2015-04
• Study Completion: 2015-04

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-04691502 + Exemestane	PF-04691502	PF-04691502 in combination with Exemestane
PF-04691502 + Exemestane	Exemestane	PF-04691502 in combination with Exemestane
Exemestane	Exemestane	Exemestane alone

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	Baseline up to month 12

Secondary Outcome Measures

Name	Time	Method
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