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:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01430585
First received: August 18, 2011
Last updated: December 21, 2012
Last verified: December 2012
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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:
Genetics Home Reference related topics:
breast cancer
Drug Information available for:
Letrozole
U.S. FDA Resources
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
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 June 17, 2013