Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02499146
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02499146
Recruitment Status : Active, not recruiting
First Posted : July 15, 2015
Last Update Posted : January 28, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 13, 2015
First Posted Date  ICMJE July 15, 2015
Last Update Posted Date January 28, 2019
Actual Study Start Date  ICMJE September 11, 2015
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
  • Single-dose PK: Maximum Observed Plasma Concentration (Cmax) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Maximum Observed Plasma Concentration (Cmax)
  • Single-dose PK: Area Under the Curve From Time Zero to Infinite (AUCinf) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Area under the plasma concentration versus time curve from time zero extrapolated to infinite time (AUCinf)
  • Single-dose PK: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    AUClast= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration
  • Single-dose PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Time for Cmax
  • Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Single-dose PK: Plasma Decay Half-Life (t1/2) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Single-dose PK: Area Under the Curve From Time Zero to the time 10 hours (AUC10) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Area under the plasma concentration versus time curve from time zero extrapolated to the time 10 hours
  • Single-dose PK: Area under the curve from time zero to the time 24 hours (AUC24) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Area under the plasma concentration versus time curve from time zero to the time 24 hours
  • Single-dose PK: Rate constant for terminal phase (Kel) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Rate constant for terminal phase calculated from the log-linear concentration-time curve
  • Single-dose PK: Mean residence time (MRT) for Palbociclib [ Time Frame: Predose, 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Mean residence time
  • Multiple-dose PK: Maximum Observed Plasma Concentration at Steady State (Css,max) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Maximum Observed Plasma Concentration (Cmax) at steady state
  • Multiple-dose PK: Area Under the Curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau)
  • Multiple-dose PK: Minimum Observed Plasma Concentration at Steady State (Css,min) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Minimum Observed Plasma Concentration at Steady State (Css,min)
  • Multiple-dose PK: Average plasma concentration at steady state (Css,av) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Average plasma concentration at steady state (Css,av)
  • Multiple-dose PK: Time to Reach Maximum Observed Plasma Concentration at steady state (Tss,max) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Time for Css,max
  • Multiple-dose PK: Apparent Volume of Distribution at steady state (Vz/F) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Multiple-dose PK: Plasma Decay Half-Life (t1/2) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Multiple-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Multiple-dose PK: Accumulation ratio (Rac) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUCss,tau) after multiple dose divided by AUC from time 0-24 after single-dose.
  • Steady state accumulation ratio (Rss) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Rss=AUCss,tau/AUCinf
  • Multiple-dose PK: Fluctuation at steady state (DF) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Peak to trough fluctuation=(Css,max-Css,min)/Css,av
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
  • Single-dose PK: Maximum Observed Plasma Concentration (Cmax) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Maximum Observed Plasma Concentration (Cmax)
  • Single-dose PK: Area Under the Curve From Time Zero to Infinite (AUCinf) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Area under the plasma concentration versus time curve from time zero extrapolated to infinite time (AUCinf)
  • Single-dose PK: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    AUClast= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration
  • Single-dose PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Time for Cmax
  • Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Single-dose PK: Plasma Decay Half-Life (t1/2) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Single-dose PK: Area Under the Curve From Time Zero to the time 10 hours (AUC10) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Area under the plasma concentration versus time curve from time zero extrapolated to the time 10 hours
  • Single-dose PK: Area under the curve from time zero to the time 24 hours (AUC24) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Area under the plasma concentration versus time curve from time zero to the time 24 hours
  • Single-dose PK: Rate constant for terminal phase (Kel) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Rate constant for terminal phase calculated from the log-linear concentration-time curve
  • Single-dose PK: Mean residence time (MRT) for Palbociclib [ Time Frame: 2, 4, 6, 8, 10, 24, 48, 72, 96, and 120 hr post dose ]
    Mean residence time
  • Multiple-dose PK: Maximum Observed Plasma Concentration at Steady State (Css,max) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Maximum Observed Plasma Concentration (Cmax) at steady state
  • Multiple-dose PK: Area Under the Curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau)
  • Multiple-dose PK: Minimum Observed Plasma Concentration at Steady State (Css,min) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Minimum Observed Plasma Concentration at Steady State (Css,min)
  • Multiple-dose PK: Average plasma concentration at steady state (Css,av) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Average plasma concentration at steady state (Css,av)
  • Multiple-dose PK: Time to Reach Maximum Observed Plasma Concentration at steady state (Tss,max) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Time for Css,max
  • Multiple-dose PK: Apparent Volume of Distribution at steady state (Vz/F) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Multiple-dose PK: Plasma Decay Half-Life (t1/2) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Multiple-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Multiple-dose PK: Accumulation ratio (Rac) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUCss,tau) after multiple dose divided by AUC from time 0-24 after single-dose.
  • Steady state accumulation ratio (Rss) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Rss=AUCss,tau/AUCinf
  • Multiple-dose PK: Fluctuation at steady state (DF) for Palbociclib [ Time Frame: Pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hr post dose ]
    Peak to trough fluctuation=(Css,max-Css,min)/Css,av
Change History Complete list of historical versions of study NCT02499146 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
  • Progression-Free Survival (PFS) [ Time Frame: 2 years ]
    Time from the Cycle 1 Day 1 of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
  • QTc [ Time Frame: 2 years ]
    Corrected QT interval
  • 1-year PFS probability [ Time Frame: 1 year ]
    The 1-year PFS probability will be estimated using the Kaplan-Meier method
  • Disease Control [ Time Frame: 2 years ]
    DCR is defined as the percent of participants with a confirmed complete response (CR), partial response (PR) or stable disease (SD) according to RECIST
  • Objective Response [ Time Frame: 2 years ]
    Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).
  • Duration of Response [ Time Frame: 2 years ]
    Time in weeks/months from the first documentation of objective tumor response to objective tumor progression or death due to any cancer
  • Trough plasma concentration of Letrozole [ Time Frame: Pre-dose time points On Day 19, 20 and 21 in Cycle 1 and on Day 1 of Cycle 2 ]
    Trough plasma concentration after multiple dose of Letrozole
  • Skin biomarker phosphorylated retinoblastoma protein (pRb) and Ki67 expression [ Time Frame: Pre-dose, 10, 24 hr after single-dose in Lead-in Phase; 10, 24, 48, 72, 96 and 120 hr post multiple dosing in Cycle 1 ]
    Samples will be collected from all enrolled patients at pre-dose on Day -1. In Lead-in phase and Cycle 1, patients will be randomized into 2 groups for different collection schedules: patients from Group 1 will be required to provide samples on Day 2 (24 hours post dose) in Lead-in phase, Days 22, 24 and 26 in Cycle 1; patients from Group 2 will be required to provide samples on Day 1 (10 hours post dose) in Lead-in phase, Days 21 (10 hours post-dose), 23 and 25 in Cycle 1.
  • Blood biomarker thymidine kinase (TK) activity [ Time Frame: Pre-dose, 4, 8, 10, 24, 72, and 120 hr post single dose in Lead-in Phase; 4, 8, 10, 24, 48, 72, 96 and 120 hr post multiple dosing in Cycle 1; at pre-dose on Cycle 2 Day 1. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Palbociclib Pharmacokinetics Study In Postmenopausal Chinese Women With ER (+), HER2 (-) Advanced Breast Cancer
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Advanced Breast Cancer
Intervention  ICMJE
  • Drug: Palbociclib
    125 mg orally once daily with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle
  • Drug: Letrozole
    2.5 mg , orally once daily (continuously)
Study Arms  ICMJE Experimental: Cohort 1
Combination therapy of palbociclib and letrozole
Interventions:
  • Drug: Palbociclib
  • Drug: Letrozole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 24, 2017)
26
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2015)
25
Estimated Study Completion Date  ICMJE January 26, 2020
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02499146
Other Study ID Numbers  ICMJE A5481019
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP