Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments pd 0332991, letrozole
Phase phase 1/phase 2
Sponsor Pfizer
Start date September 2008
End date November 2013
Trial size 177 participants
Trial identifier NCT00721409, 2008-002392-27, A5481003

Summary

The study is aimed to confirm that letrozole + PD 0332991 is safe and tolerable and to assess the effect of the combination on advanced breast cancer

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
letrozole + PD 0332991
pd 0332991
125 mg/d capsules orally for 3 out of 4 weeks in repeated cycles
letrozole
2.5 mg/d tablets orally on a continuous regimen
(Active Comparator)
letrozole
letrozole
2.5 mg/d tablets orally on a continuous regimen

Primary Outcomes

Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1
time frame: Maximum treatment duration (approximately 55 months)
Number of Participants With Treatment-Related Adverse Events at Phase 1
time frame: Maximum treatment duration (approximately 55 months)
Number of Participants With Dose Limiting Toxicities at Phase 1
time frame: Cycle 2 (4 weeks)
Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment
time frame: From randomization date to date of first documentation of progression or death (assessed up to 41 months)

Secondary Outcomes

Measure
Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1
time frame: From Baseline up to end of study (assessed up to 55 months)
Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1
time frame: From Baseline up to end of study (assessed up to 55 months)
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1
time frame: Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1
time frame: Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1
time frame: Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Terminal Plasma Half-life (t1/2) at Phase 1
time frame: Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1
time frame: Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Volume of Distribution (Vz/F) at Phase 1
time frame: Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1
time frame: Cycle 2 Day 14, Cycle 2 Day 28
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1
time frame: Cycle 2 Day 14, and Cycle 2 Day 28
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1
time frame: Cycle 2 Day 14, and Cycle 2 Day 28
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1
time frame: Cycle 1 Day 1 prior to dosing, Cycle 1 Day 14 (2, 4 [prior to meal], 8, 24, 48, and 96 hours after dosing of Palbociclib), Cycle 2 Day 1 and Day 14 (prior to and 4 hours after dosing of letrozole)
Overall Survival (OS) at Phase 2
time frame: From randomization until death (assessed up to 41 months)
Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment
time frame: From randomization up to the end of treatment (approximately 41 months)
Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment
time frame: From randomization up to the end of treatment (approximately 41 months)
Duration of Response at Phase 2 - Investigator Assessment
time frame: From randomization up to the end of treatment (approximately 41 months)
Number of Participants With CBR at Phase 2 - Investigator Assessment
time frame: From randomization up to the end of treatment (approximately 41 months)
Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment
time frame: From randomization up to the end of treatment (approximately 41 months)
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2
time frame: Baseline, End of treatment (approximately 41 months)
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2
time frame: Baseline, End of treatment (approximately 41 months)
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1
time frame: Screening visit (≤ 28 Days prior to dosing)
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67
time frame: Screening visit (≤ 28 Days prior to dosing)
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1
time frame: Screening visit (≤ 28 Days prior to dosing)
Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2
time frame: Screening visit (≤ 28 Days prior to dosing)
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2
time frame: Screening visit (≤ 28 Days prior to dosing)
Number of Participants With TEAEs (All Causalities) at Phase 2
time frame: Maximum treatment duration (approximately 41 months)
Number of Participants With Treatment-Related Adverse Events at Phase 2
time frame: Maximum treatment duration (approximately 41 months)

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Inoperable estrogen receptor positive and HER2 negative breast cancer. - Postmenopausal status. - Tumor tissue (archived acceptable) available for biomarker studies. For Phase 2 Part 2 - CCND1 amplification and/or loss of p16 as determined by the central laboratory. - Acceptable bone marrow, liver and kidney function. Exclusion Criteria: - Prior or concomitant treatment for advanced breast cancer. - Other major cancer in the past 3 years. - Important cardiovascular events in the past 6 months.

Additional Information

Official title Phase 1/2, Open-label, Randomized Study Of The Safety, Efficacy, And Pharmacokinetics Of Letrozole Plus Pd 0332991 (Oral Cdk 4/6 Inhibitor) And Letrozole Single Agent For The First-line Treatment Of Er Positive, Her2 Negative Advanced Breast Cancer In Postmenopausal Women
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Pfizer.