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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01658176
First received: July 16, 2012
Last updated: October 26, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Breast Neoplasms
Drug: PF-04691502
Drug: Exemestane
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Baseline up to month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective tumor response using RECIST [ Time Frame: Baseline up to month 12 ] [ Designated as safety issue: No ]
  • Duration of tumor response [ Time Frame: Baseline up to month 12 ] [ Designated as safety issue: No ]
  • Clinical benefit response [ Time Frame: Baseline up to month 12 ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Biomarkers related to PI3K/mTOR signal deregulation and markers of cellular proliferation and apoptosis in primary tumor tissue [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of single dose of PF-04691502 [ Time Frame: Day 2 Pre-dose, and 1 , 2, 4 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of single dose exemestane [ Time Frame: Day 1 pre-dose, and 1, 2, 4 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of PF-04691502 and exemestane when administered in combination [ Time Frame: Day 8 Pre-dose, and 1, 2, 4 and 24 hours post-dose, Weel 5, 9, 13, 17, 21, and 25 ] [ Designated as safety issue: No ]
  • Pharmacodynamic endpoints including serum glucose, insulin, HbA1c, cholesterol and triglycerides [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Heath related quality of life measured by Functional Assessment of Cancer Therapy- Breast [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) of single dose of PF-04691502 [ Time Frame: Day 2 Pre-dose, and 1 , 2, 4 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) of single dose exemestane [ Time Frame: Day 1 pre-dose, and 1, 2, 4 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) of PF-04691502 and exemestane when administered in combination [ Time Frame: Day 8 Pre-dose, and 1, 2, 4 and 24 hours post-dose, Weel 5, 9, 13, 17, 21, and 25 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01658176

Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01658176     History of Changes
Other Study ID Numbers: B1271005
Study First Received: July 16, 2012
Last Updated: October 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Estrogen receptor positive
Her-2 negative
advanced breast cancer
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Sirolimus
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014