Clinical trial NCT01430585: Pre-Operative Study of PF-4691502 With Letrozole Compared To Letrozole Alone In Patients With Early Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Early Breast Cancer (Phase 2)
Advanced Breast Cancer (Phase 1b)
Keywords: Ki-67
postmenopausal early breast cancer
ER positive/HER2 negative early breast cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-09-08
Enrollment: 14
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 1B
timeFrame: Phase 1B: Baseline up to 28 days after last administration of study treatment
measure: Change From Baseline in Ki-67 Percent Positive Tumor Cells in Biopsied Tumor Tissue at Week 6: Phase 2
timeFrame: Phase 2: Baseline, Week 6
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 2
timeFrame: Phase 2: Baseline up to 28 days after last administration of study treatment
measure: Number of Participants With Clinically Significant Laboratory Tests Abnormalities: Phase 1B and 2
timeFrame: Phase 1B: Baseline up to end of treatment (Week 34); Phase 2: Baseline up to Week 16 or early termination (ET)
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs: Phase 1B and 2
timeFrame: Phase 1B: Baseline up to 28 days after last dose of study treatment (Week 34); Phase 2: Baseline up to Week 16 or ET
measure: Number of Participants With Clinically Significant Abnormalities in Corrected QT (QTc) Interval: Phase 1B
timeFrame: Phase 1B: Baseline up to end of treatment (Week 34)
measure: Number of Participants With Objective Response (OR): Phase 1B and 2
timeFrame: Phase 1B: Baseline, Week 12, end of treatment (Week 34); Phase 2: Baseline, Week 6, 16 or ET
measure: Pharmacokinetic (PK) Parameters of PF-04691502 and Letrozole: Phase 1B and 2
timeFrame: Phase 1B: 0 (pre-dose), 1, 2, 4, 6, 24 hours on Day 1 (letrozole alone), Day 2 (PF-0491502 alone), Day 12, Week 5 (PF-0491502 and letrozole in combination); Phase 2: 0 (pre-dose), 1, 2, 4, 6, 24 hours on Day 1, pre-dose on Week 2, 6
measure: Change From Baseline in Pharmacodynamic, Cell Proliferation and Survival Biomarkers in Biopsied Tumor Tissue at Week 2 and 6: Phase 2
timeFrame: Phase 2: Baseline, Week 2, 6
measure: Number of Participants With Genetic Alterations: Phase 2
timeFrame: Phase 2: Baseline, Week 2, 6
Other outcomes:
Locations:
city: Charleroi
country: Belgium
facility: Pfizer Investigational Site
city: Milano
country: Italy
facility: Pfizer Investigational Site
city: Barcelona
country: Spain
facility: Pfizer Investigational Site
city: Goteborg
country: Sweden
facility: Pfizer Investigational Site
city: Stockholm
country: Sweden
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: