Palbociclib Pharmacokinetics Study In Postmenopausal Chinese Women With ER (+), HER2 (-) Advanced Breast Cancer

NCT02499146 | Completed Phase 1 Results

• 2 other identifiers: A5481019NCT02499146
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 7

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.

Conditions

Advanced Breast Cancer

Keywords

Palbociclib; PD-0332991; pharmacokinetics; breast cancer patients; Chinese

Outcome Measures

Primary Outcomes (22)

• Single-dose Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Palbociclib

  Cmax of palbociclib in the single-dose part (lead-in phase) was observed directly from data.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Time to Reach Maximum Plasma Concentration (Tmax) for Palbociclib

  Tmax for palbociclib in the single-dose part (lead-in phase) was observed directly from data as time of first occurrence.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Time 10 Hours (AUC10) for Palbociclib

  AUC10 for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, and 10 hours post dose

• Single-dose PK: AUC From Time 0 to the Time 24 Hours (AUC24) for Palbociclib

  AUC24 is AUCtau, where the dosing interval (tau) is 24 hours. AUC24 in the single-dose part (lead-in phase) for palbociclib was obtained by linear/log trapezoidal method.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, and 24 hours post dose

• Single-dose PK: AUC From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Palbociclib

  AUClast for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Palbociclib

  AUCinf for palbociclib in the single-dose part (lead-in phase) was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the rate constant for terminal phase obtained by linear regression of the log-linear concentration-time curve.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Rate Constant for Terminal Phase (Kel) for Palbociclib

  Kel for palbociclib in the single-dose part (lead-in phase) was obtained by linear regression of the log-linear concentration-time curve.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Mean Residence Time (MRT) for Palbociclib

  MRT for palbociclib in the single-dose part (lead-in phase) was calculated as AUMCinf/AUCinf, where AUMCinf was area under the first moment curve from time 0 to infinity.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Terminal Half-Life (t1/2) for Palbociclib

  t1/2 for palbociclib in the single-dose part (lead-in phase) was calculated as Loge(2)/kel.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib

  CL/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/AUCinf.

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib

  Vz/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/(AUCinf \* kel).

  Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose

• Multiple-dose PK: Maximum Plasma Concentration at Steady State (Css,Max) for Palbociclib

  Css,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.

  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

• Multiple-dose PK: Minimum Plasma Concentration at Steady State (Css,Min) for Palbociclib

  Css,min of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.

  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

• Multiple-dose PK: AUC Within a Dosing Interval of Tau (=24 Hours) at Steady State (AUCss,Tau) for Palbociclib

  AUCss,tau of palbociclib in the multiple-dose part (Cycle 1) was determined by linear/log trapezoidal method.

  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

• Multiple-dose PK: Average Plasma Concentration at Steady State (Css,av) for Palbociclib

  Css,av of palbociclib in the multiple-dose part (Cycle 1) was calculated as AUCss,tau/tau, where tau was 24 hours.

  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

• Multiple-dose PK: Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for Palbociclib

  Tss,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data as time of first occurrence within tau (=24 hours) at steady state.

  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

• Multiple-dose PK: Vz/F for Palbociclib

  Vz/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/(AUCss,tau \* kel), where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state and kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.

  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

• Multiple-dose PK: t1/2 for Palbociclib

  t1/2 of palbociclib in the multiple-dose part (Cycle 1) was calculated as ln (2)/kel, where kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.

  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

• Multiple-dose PK: CL/F for Palbociclib

  CL/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/AUCss,tau, where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state.

  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

• Multiple-dose PK: Peak to Trough Fluctuation at Steady State (PTF) for Palbociclib

  PTF of palbociclib in the multiple-dose part (Cycle 1) was determined as (Css,max - Css,min)/Css,av. Css,max and Css,min were observed directly from data while Css,av was calculated as AUCss,tau/tau, where tau was 24 hours.

  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

• Observed Accumulation Ratio (Rac) for Palbociclib

  Rac of palbociclib was determined as AUCss,tau/AUCsd,tau, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCsd,tau was AUC24 from single-dose part (lead-in phase).

  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

• Steady State Accumulation Ratio (Rss) for Palbociclib

  Rss of palbociclib was calculated as AUCss,tau/AUCinf, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCinf was from single-dose part (lead-in phase).

  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 (13)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From first dose of study medication up to 28 days after last dose of study medication (up to maximum of 475 weeks, maximum treatment exposure = 471 weeks)

• Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade

  From first dose of study medication up to 28 days after last dose of study medication (up to maximum of 475 weeks, maximum treatment exposure = 471 weeks)

• Number of Participants With Laboratory Test Abnormalities

  From first dose of study medication up to 28 days after last dose of study medication (up to maximum of 475 weeks, maximum treatment exposure = 471 weeks)

• Number of Participants Meeting the Categorical Summarization Criteria for QTcF and QTcB Parameters

  From first dose of study medication up to 28 days after last dose of study medication (up to maximum of 475 weeks, maximum treatment exposure = 471 weeks)

• Progression-Free Survival (PFS)

  From C1D1 to date of first documentation of PD or death due to any cause, whichever occurred first (up to maximum of 471 weeks of treatment exposure)

Study Arms (1)

Cohort 1

EXPERIMENTAL

Combination therapy of palbociclib and letrozole

Drug: Palbociclib; Drug: Letrozole

Interventions

Palbociclib DRUG

125 mg orally once daily with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle

Cohort 1

Letrozole DRUG

2.5 mg , orally once daily (continuously)

Cohort 1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (7)

Beijing Cancer Hospital/Oncology department

Beijing, Beijing Municipality, 100142, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Guangdong General Hospital/Department of Breast Surgery

Guangzhou, Guangdong, 510080, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

Location

The first hospital of jilin university

Changchun, Jilin, 130021, China

Location

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

Related Publications (2)

• 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.

  PMID: 34554584 DERIVED

• 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.

  PMID: 33835229 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

palbociclib; Letrozole

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2015
• First Posted: July 15, 2015
• Study Start: September 11, 2015
• Primary Completion: July 31, 2018
• Study Completion: December 24, 2024
• Last Updated: February 11, 2026
• Results First Posted: July 29, 2019

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)