Clinical trial NCT02499146: Palbociclib Pharmacokinetics Study In Postmenopausal Chinese Women With ER (+), HER2 (-) Advanced Breast Cancer
Official title: A PHASE 1 OPEN-LABEL PHARMACOKINETICS STUDY OF PALBOCICLIB, A CYCLIN-DEPENDENT KINASE 4 AND 6 (CDK4/6) INHIBITOR, IN POSTMENOPAUSAL CHINESE WOMEN WITH ER (+), HER2 (-) ADVANCED BREAST CANCER
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Breast Cancer
Keywords: Palbociclib
PD-0332991
pharmacokinetics
breast cancer patients
Chinese
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-07-15
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Primary purpose: OTHER

Brief 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.


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).

Primary outcomes:
measure: Single-dose Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Time to Reach Maximum Plasma Concentration (Tmax) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Time 10 Hours (AUC10) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, and 10 hours post dose
measure: Single-dose PK: AUC From Time 0 to the Time 24 Hours (AUC24) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, and 24 hours post dose
measure: Single-dose PK: AUC From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Rate Constant for Terminal Phase (Kel) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Mean Residence Time (MRT) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Terminal Half-Life (t1/2) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose
measure: Multiple-dose PK: Maximum Plasma Concentration at Steady State (Css,Max) for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
measure: Multiple-dose PK: Minimum Plasma Concentration at Steady State (Css,Min) for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
measure: Multiple-dose PK: AUC Within a Dosing Interval of Tau (=24 Hours) at Steady State (AUCss,Tau) for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
measure: Multiple-dose PK: Average Plasma Concentration at Steady State (Css,av) for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
measure: Multiple-dose PK: Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
measure: Multiple-dose PK: Vz/F for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
measure: Multiple-dose PK: t1/2 for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
measure: Multiple-dose PK: CL/F for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
measure: Multiple-dose PK: Peak to Trough Fluctuation at Steady State (PTF) for Palbociclib
timeFrame: Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24, 48, 72, 96, 120 hours post dose on Day 21
measure: Observed Accumulation Ratio (Rac) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, and 24 hours post dose; Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, and 24 hours post dose on Day 21
measure: Steady State Accumulation Ratio (Rss) for Palbociclib
timeFrame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose; Cycle 1: pre-dose on Day 19, Day 20, Day 21, and 2, 4, 6, 8, 10, 24 hours post dose on Day 21
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study medication up to 28 days after last dose (up to 2.8 years by primary completion date of 31 July 2018)
measure: Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade
timeFrame: up to 2.8 years by primary completion date of 31 July 2018
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: up to 2.8 years by primary completion date of 31 July 2018
measure: Number of Participants Meeting the Categorical Summarization Criteria for QTcF and QTcB Parameters
timeFrame: up to 2.8 years by primary completion date of 31 July 2018
measure: Progression-Free Survival (PFS)
timeFrame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
measure: Percentage of Participants Achieving Objective Response (Objective Response Rate [ORR])
timeFrame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
measure: Percentage of Participants Achieving Disease Control (Disease Control Rate [DCR])
timeFrame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
measure: Duration of Response
timeFrame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018
measure: 1-Year PFS Probability
timeFrame: 1 year
measure: Trough Plasma Concentration of Letrozole
timeFrame: pre-dose of Cycle 1 Days 19, 20, 21 and Cycle 2 Day 1
measure: Ratio Over Baseline for Skin Biomarker Phosphorylated Retinoblastoma Protein (pRb) Expression
timeFrame: Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26
measure: Ratio Over Baseline for Skin Biomarker Ki67 Expression
timeFrame: Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26
measure: Ratio Over Baseline for Thymidine Kinase (TK) Concentration
timeFrame: Baseline (Day -1 pre-dose), lead-in phase Day 1 (4, 8, 10, 24, 72, 120 hours post dose), Cycle 1 Day 21 (4, 8, 10, 24, 72, 96, 120 hours post dose), Cycle 2 Day 1 pre-dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital/Oncology department
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital/Department of Breast Surgery
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Changchun
country: China
facility: The first hospital of jilin university
state: Jilin
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine, Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Yu Y, Sun W, Liu Y, Wang D. Pharmacodynamic Modeling of CDK4/6 Inhibition-Related Biomarkers and the Characterization of the Relationship Between Biomarker Response and Progression-Free Survival in Patients With Advanced Breast Cancer. J Clin Pharmacol. 2022 Mar;62(3):376-384. doi: 10.1002/jcph.1971. Epub 2021 Nov 16.
citation: Xu B, Li H, Zhang Q, Sun W, Yu Y, Li W, Wang S, Liao N, Shen P, Liu Y, Huang Y, Linn C, Zhao H, Jiang J, Wang D. Pharmacokinetics, safety, activity, and biomarker analysis of palbociclib plus letrozole as first-line treatment for ER+/HER2- advanced breast cancer in Chinese women. Cancer Chemother Pharmacol. 2021 Jul;88(1):131-141. doi: 10.1007/s00280-021-04263-9. Epub 2021 Apr 9.