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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: PF-04691502; Drug: Exemestane

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	2 years
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
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): April 1, 2015
• Study Completion (Anticipated): April 1, 2015

Study Registration Dates

• First Submitted: July 16, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (Estimate): August 6, 2012

Study Record Updates

• Last Update Posted (Estimate): October 29, 2012
• Last Update Submitted That Met QC Criteria: October 26, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Breast Cancer; advanced breast cancer; Estrogen receptor positive; Her-2 negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: B1271005