Phase 1
Completed N=26
Palbociclib Pharmacokinetics Study In Postmenopausal Chinese Women With ER (+), HER2 (-) Advanced Breast Cancer
Source: ClinicalTrials.gov NCT02499146 ↗Enrolled (actual)
26
Serious AEs
15.4%
Results posted
Jul 2019
Primary outcomePrimary: Single-dose Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Palbociclib — 82.14 nanograms per milliliter (ng/mL)
Summary
As part of the global clinical development program for Palbociclib, studies are planned in cancer patients in China. An assessment of Palbociclib pharmacokinetics in Chinese patients, as required by the Chinese Health Authorities, is therefore warranted. In addition, safety and efficacy will be also evaluated.
The single and multiple 125 mg oral dose pharmacokinetics of Palbociclib will be characterized.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Single-dose Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Palbociclib |
82.14 | — |
| PRIMARY Single-dose PK: Time to Reach Maximum Plasma Concentration (Tmax) for Palbociclib |
7.94 | — |
| PRIMARY Single-dose PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Time 10 Hours (AUC10) for Palbociclib |
498.3 | — |
| PRIMARY Single-dose PK: AUC From Time 0 to the Time 24 Hours (AUC24) for Palbociclib |
1217 | — |
| PRIMARY Single-dose PK: AUC From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Palbociclib |
2308 | — |
| PRIMARY Single-dose PK: AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Palbociclib |
2386 | — |
| PRIMARY Single-dose PK: Rate Constant for Terminal Phase (Kel) for Palbociclib |
0.03006 | — |
| PRIMARY Single-dose PK: Mean Residence Time (MRT) for Palbociclib |
34.42 | — |
| PRIMARY Single-dose PK: Terminal Half-Life (t1/2) for Palbociclib |
23.46 | — |
| PRIMARY Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib |
52.40 | — |
| PRIMARY Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib |
1758 | — |
| PRIMARY Multiple-dose PK: Maximum Plasma Concentration at Steady State (Css,Max) for Palbociclib |
139.7 | — |
| PRIMARY Multiple-dose PK: Minimum Plasma Concentration at Steady State (Css,Min) for Palbociclib |
67.55 | — |
| PRIMARY Multiple-dose PK: AUC Within a Dosing Interval of Tau (=24 Hours) at Steady State (AUCss,Tau) for Palbociclib |
2501 | — |
| PRIMARY Multiple-dose PK: Average Plasma Concentration at Steady State (Css,av) for Palbociclib |
104.2 | — |
| PRIMARY Multiple-dose PK: Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for Palbociclib |
6.05 | — |
| PRIMARY Multiple-dose PK: Vz/F for Palbociclib |
1910 | — |
| PRIMARY Multiple-dose PK: t1/2 for Palbociclib |
27.26 | — |
| PRIMARY Multiple-dose PK: CL/F for Palbociclib |
49.97 | — |
| PRIMARY Multiple-dose PK: Peak to Trough Fluctuation at Steady State (PTF) for Palbociclib |
0.6652 | — |
| PRIMARY Observed Accumulation Ratio (Rac) for Palbociclib |
2.042 | — |
| PRIMARY Steady State Accumulation Ratio (Rss) for Palbociclib |
1.036 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
26; 26; 4; 1 | — |
| SECONDARY Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade |
0; 5; 16; 5; 0 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities |
23; 19; 26; 20; 25; 11 | — |
| SECONDARY Number of Participants Meeting the Categorical Summarization Criteria for QTcF and QTcB Parameters |
21; 4; 1; 0; 17; 9 | — |
| SECONDARY Progression-Free Survival (PFS) |
18.6 | — |
| SECONDARY Percentage of Participants Achieving Objective Response (Objective Response Rate [ORR]) |
19.2 | — |
| SECONDARY Percentage of Participants Achieving Disease Control (Disease Control Rate [DCR]) |
65.4 | — |
| SECONDARY Duration of Response |
25.1 | — |
| SECONDARY 1-Year PFS Probability |
57.5 | — |
| SECONDARY Trough Plasma Concentration of Letrozole |
83.70; 83.85; 85.30; 97.40 | — |
| SECONDARY Ratio Over Baseline for Skin Biomarker Phosphorylated Retinoblastoma Protein (pRb) Expression |
0.644; 0.523; 0.535; 0.773; 0.799; 1.493 | — |
| SECONDARY Ratio Over Baseline for Skin Biomarker Ki67 Expression |
0.985; 0.868; 0.495; 0.408; 0.599; 0.832 | — |
| SECONDARY Ratio Over Baseline for Thymidine Kinase (TK) Concentration |
0.780; 0.774; 0.733; 0.702; 0.530; 0.598 | — |
Eligibility Criteria
Inclusion Criteria
- ER(+), HER2(-), postmenopausal adult (ages 18-65 years, inclusive) Chinese women with proven diagnosis of adenocarcinoma of the breast with evidence locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
a. Postmenopausal women: i. Prior bilateral surgical oophorectomy; or ii. Medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause b. Documentation of histologically or cytologically confirmed diagnosis of: i. ER(+) breast cancer. c. Documentation of HER2(-) breast cancer. d. Previously untreated with any systemic anti cancer therapy for their locoregionally recurrent or metastatic ER+ disease.
- Measurable disease as defined per RECIST v.1.1 or bone-only disease. - Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented.
Exclusion Criteria
- HER2-positive tumor as defined by documentation of erbB-2 gene amplification by FISH (as defined by a HER2/CEP17 ratio ≥2) or chromogenic in situ hybridization (CISH, as defined by the manufacturer's kit instruction) or documentation of HER2 overexpression by IHC (defined as IHC3+, or IHC2+ with FISH or CISH confirmation) based on local laboratory results
- Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
Data sourced from ClinicalTrials.gov (NCT02499146). 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.