Pre-Operative Study of PF-4691502 With Letrozole Compared To Letrozole Alone In Patients With Early Breast Cancer

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01430585
First received: August 18, 2011
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

PF-04691502 is an inhibitor of PI3K and mTOR kinase. Published data support the hypothesis that a PI3K/mTOR antagonist in combination with letrozole might mitigate the intrinsic or acquired resistance to hormonal therapy and restore hormone sensitivity in high risk (high Ki-67) patient population of hormone-sensitive breast cancers. In addition, Ki-67, a marker of cellular proliferation, could be used to select those patients who benefit from treatment with a PI3K-pathway inhibitor.


Condition Intervention Phase
Early Breast Cancer (Phase 2)
Advanced Breast Cancer (Phase 1b)
Drug: PF-04691502
Drug: PF-04691502 in combination with Letrozole
Drug: Letrozole
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, Randomised Phase 1b/2 Study Of PF-04691502 In Combination With Letrozole Compared With Letrozole Alone In Patients With Estrogen Receptor Positive, Her-2 Negative Early Breast Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change in biopsied tumor tissue from Baseline in Ki-67 (% positive tumor cells) at 6 weeks (Phase 2) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • QTc Interval (Phase 1b) [ Time Frame: Days 1, 2, 12 during PK assessment in Phase 1b portion of the study ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) - single-dose PF-04691502 (Phase 1b) [ Time Frame: Pre-dose and at 1, 2, 4, 6 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) - single-dose PF-04691502 (Phase 1b) [ Time Frame: Pre-dose and at 1, 2, 4, 6 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) of PF-04691502 at steady-state (Phase 1b) [ Time Frame: Day 12 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) of PF-04691502 at steady-state (Phase 1b) [ Time Frame: Day 12 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) - single-dose PF-04691502 (Phase 2) [ Time Frame: Pre-dose and at 1, 2, 4 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma concentration versus time curve (AUC) - Single-dose PF-04691502 (Phase 2) [ Time Frame: Pre-dose and at 1, 2, 4 and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Change in biopsied tumor tissue from Baseline in phosphorylated-AKT(S473 epitope) at 2 weeks (Phase 2) [ Time Frame: Baseline and Week 2 ] [ Designated as safety issue: No ]
  • Change in biopsied tumor tissue from Baseline in phosphorylated-AKT(S473 epitope) at 6 weeks (Phase 2) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Change in biopsied tumor tissue from Baseline in phosphorylated-S6 at 2 weeks (Phase 2) [ Time Frame: Baseline and Week 2 ] [ Designated as safety issue: No ]
  • Change in biopsied tumor tissue from Baseline in phosphorylated-S6 at 6 weeks (Phase 2) [ Time Frame: Baseline and Week 6 ] [ Designated as safety issue: No ]
  • Objective tumor response (Phase 1b and 2) [ Time Frame: 12 months (Phase 1b); Week 6 (Phase 2) ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: March 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: PF-04691502
PF-04691502 administered as single agent for 2 weeks. After this period, patients in this arm will take PF-04691502 in combination with Letrozole until Week 6. Beyond Week 6, if considered appropriate, patients can be treated with the combination for up to 10 additional weeks until breast surgery.
Experimental: B Drug: PF-04691502 in combination with Letrozole
PF-04691502 in combination with Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery.
Active Comparator: C Drug: Letrozole
Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery.

Detailed Description:

The study was prematurely discontinued on 09Oct2012 due to the tolerability findings in 2 clinical studies testing PF-04691502 that have prompted the Sponsor to re-evaluate the strategic goals of the program. In the study B1271003 an unexpected frequency of severe skin toxicity was observed and in the study B1271004 5 cases of drug induced pneumonitis were reported.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Phase 1 - Postmenopausal women with diagnosis of breast cancer, metastatic disease or locally advanced disease / Estrogen Receptor positive and HER-2 negative / candidate to receive Letrozole
  • Phase 2 - Postmenopausal women with newly diagnosed primary breast cancer / Estrogen Receptor positive and HER-2 negative / Ki-67 levels >10% positive cells
  • Phase 1 & 2 - Glucose control, adequate bone marrow, liver, renal, and cardiac function

Exclusion Criteria:

  • Inflammatory carcinoma / Prior therapy with an agent active on PI3K and/or mTOR / 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: NCT01430585

Locations
Belgium
Pfizer Investigational Site
Charleroi, Belgium, 6000
Italy
Pfizer Investigational Site
Milano, Italy, 20132
Spain
Pfizer Investigational Site
Barcelona, Spain, 08035
Sweden
Pfizer Investigational Site
Goteborg, Sweden, 413 45
Pfizer Investigational Site
Stockholm, Sweden, 171 76
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: NCT01430585     History of Changes
Other Study ID Numbers: B1271003
Study First Received: August 18, 2011
Last Updated: December 21, 2012
Health Authority: United Kingdon: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Pfizer:
Ki-67
postmenopausal early breast cancer
ER positive/HER2 negative early breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014