Phase 2
Completed N=177
Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer
Source: ClinicalTrials.gov NCT00721409 ↗Enrolled (actual)
177
Serious AEs
17.5%
Results posted
Mar 2015
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 — 12; 2; 11; 0 Participants
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 |
12; 2; 11; 0 | — |
| PRIMARY Number of Participants With Treatment-Related Adverse Events at Phase 1 |
12; 0; 11; 0 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicities at Phase 1 |
2; 1 | — |
| PRIMARY Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment |
20.2; 10.2; 26.1; 5.7; 18.1; 11.1 | 0.0004 sig |
| SECONDARY Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1 |
33.3 | — |
| SECONDARY Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1 |
83.3 | — |
| SECONDARY 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 |
1982; 1933 | — |
| SECONDARY Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1 |
115.8; 108.4 | — |
| SECONDARY 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 |
7.92; 7.92 | — |
| SECONDARY 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 |
28.81; NA | — |
| SECONDARY Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1 |
63.08; NA | — |
| SECONDARY 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 |
2583; NA | — |
| SECONDARY Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1 |
1739; 1936 | — |
| SECONDARY Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1 |
94.95; 104.0 | — |
| SECONDARY Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1 |
2.00; 1.04 | — |
| SECONDARY Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 |
9; 3; 0; 11; 1; 0 | — |
| SECONDARY Overall Survival (OS) at Phase 2 |
37.5; 34.5; 37.5; 33.3; 35.1; 35.7 | 0.2812 |
| SECONDARY Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment |
42.9; 33.3; 44.1; 25.0; 42.0; 38.8 | 0.1347 |
| SECONDARY Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment |
55.4; 39.4; 55.6; 34.8; 55.3; 41.9 | 0.0471 sig |
| SECONDARY Duration of Response at Phase 2 - Investigator Assessment |
20.3; 11.1; 20.9; 10.8; 20.2; 14.8 | — |
| SECONDARY Number of Participants With CBR at Phase 2 - Investigator Assessment |
81.0; 58.0; 76.5; 43.8; 84.0; 67.3 | 0.0009 sig |
| SECONDARY Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment |
20.2; 10.2; 26.1; 5.7; 18.8; 11.1 | <0.0001 sig |
| SECONDARY Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 |
0.6; 0.1; 0.2; 0.0; 1.2; 0.1 | 0.6900 |
| SECONDARY Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 |
1.1; 0.2; 1.0; 0.2; 1.2; 0.3 | 0.3346 |
| SECONDARY Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1 |
12; 9; 39; 44; 0; 2 | — |
| SECONDARY Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67 |
26; 31; 7; 16; 19; 15 | — |
| SECONDARY Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 |
41; 32; 10; 16; 31; 16 | — |
| SECONDARY Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2 |
2.76; 2.73; 0.83; 0.87 | — |
| SECONDARY Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 |
7.9; 5.4; 10.0; 10.7; 6.5; 2.2 | — |
| SECONDARY Number of Participants With TEAEs (All Causalities) at Phase 2 |
83; 66; 33; 25; 50; 41 | — |
| SECONDARY Number of Participants With Treatment-Related Adverse Events at Phase 2 |
78; 33; 32; 13; 46; 20 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT00721409). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.