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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 : Unknown
Verified May 2019 by Pfizer.
Recruitment status was:  Active, not recruiting
First Posted : July 15, 2015
Results First Posted : July 29, 2019
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 13, 2015
First Posted Date  ICMJE July 15, 2015
Results First Submitted Date  ICMJE May 28, 2019
Results First Posted Date  ICMJE July 29, 2019
Last Update Posted Date July 29, 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: May 28, 2019)
  • Single-dose Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    Cmax of palbociclib in the single-dose part (lead-in phase) was observed directly from data.
  • Single-dose PK: Time to Reach Maximum Plasma Concentration (Tmax) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    Tmax for palbociclib in the single-dose part (lead-in phase) was observed directly from data as time of first occurrence.
  • Single-dose PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to the Time 10 Hours (AUC10) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, and 10 hours post dose ]
    AUC10 for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.
  • Single-dose PK: AUC From Time 0 to the Time 24 Hours (AUC24) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, and 24 hours post dose ]
    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.
  • Single-dose PK: AUC From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    AUClast for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.
  • Single-dose PK: AUC From Time 0 Extrapolated to Infinite Time (AUCinf) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    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.
  • Single-dose PK: Rate Constant for Terminal Phase (Kel) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    Kel for palbociclibo in the single-dose part (lead-in phase) was obtained by linear regression of the log-linear concentration-time curve.
  • Single-dose PK: Mean Residence Time (MRT) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    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.
  • Single-dose PK: Terminal Half-Life (t1/2) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    t1/2 for palbociclib in the single-dose part (lead-in phase) was calculated as Loge(2)/kel.
  • Single-dose PK: Apparent Oral Clearance (CL/F) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    CL/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/AUCinf.
  • Single-dose PK: Apparent Volume of Distribution (Vz/F) for Palbociclib [ Time Frame: Lead-in phase: Day 1 pre-dose, 2, 4, 6, 8, 10, 24, 48, 72, 96 and 120 hours post dose ]
    Vz/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/(AUCinf * kel).
  • Multiple-dose PK: Maximum Plasma Concentration at Steady State (Css,Max) for Palbociclib [ Time Frame: 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 ]
    Css,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.
  • Multiple-dose PK: Minimum Plasma Concentration at Steady State (Css,Min) for Palbociclib [ Time Frame: 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 ]
    Css,min of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.
  • Multiple-dose PK: AUC Within a Dosing Interval of Tau (=24 Hours) at Steady State (AUCss,Tau) for Palbociclib [ Time Frame: 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 ]
    AUCss,tau of palbociclib in the multiple-dose part (Cycle 1) was determined by linear/log trapezoidal method.
  • Multiple-dose PK: Average Plasma Concentration at Steady State (Css,av) for Palbociclib [ Time Frame: 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 ]
    Css,av of palbociclib in the multiple-dose part (Cycle 1) was calculated as AUCss,tau/tau, where tau was 24 hours.
  • Multiple-dose PK: Time to Reach Maximum Plasma Concentration at Steady State (Tss,Max) for Palbociclib [ Time Frame: 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 ]
    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.
  • Multiple-dose PK: Vz/F for Palbociclib [ Time Frame: 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 ]
    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.
  • Multiple-dose PK: t1/2 for Palbociclib [ Time Frame: 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 ]
    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.
  • Multiple-dose PK: CL/F for Palbociclib [ Time Frame: 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 ]
    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.
  • Multiple-dose PK: Peak to Trough Fluctuation at Steady State (PTF) for Palbociclib [ Time Frame: 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 ]
    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.
  • Observed Accumulation Ratio (Rac) for Palbociclib [ Time Frame: 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 ]
    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).
  • Steady State Accumulation Ratio (Rss) for Palbociclib [ Time Frame: 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 ]
    Rss of palbociclib was calcualted 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).
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
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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) ]
    An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. Causality to study treatment was determined by the investigator.
  • Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade [ Time Frame: up to 2.8 years by primary completion date of 31 July 2018 ]
    Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by NCI CTCAE version 4.0: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: up to 2.8 years by primary completion date of 31 July 2018 ]
    The number of participants with the following laboratory test abnormalities meeting any of the Grades 1 to 4 criteria per the NCI CTCAE (version 4.0) was summarized: anemia, lymphopenia, neutropenia, platelet count decreased, white blood cell (WBC) decreased, alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, bilirubin (total) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia.
  • Number of Participants Meeting the Categorical Summarization Criteria for QTcF and QTcB Parameters [ Time Frame: up to 2.8 years by primary completion date of 31 July 2018 ]
    QT interval (time from electrocardiogram [ECG] Q wave to the end of the T wave corresponding to electrical systole) corrected for heart rate using Fridericia's formula was QTcF and QT interval corrected for heart rate using Bazett's formula was QTcB. Categorical summarization criteria for QTcF and QTcB were as follows: 1) maximum absolute value of <450 msec, 450 to 480 msec, 481 to 500 msec, or >=500 msec; 2) maximum increase from baseline of <30 msec, 30 to <60 msec, or >=60 msec.
  • Progression-Free Survival (PFS) [ Time Frame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018 ]
    PFS was defined as the time from Cycle 1 Day 1 to date of first documentation of disease progression (PD) or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1). Objective status of PD was defined as a >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm; or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new lesions.
  • Percentage of Participants Achieving Objective Response (Objective Response Rate [ORR]) [ Time Frame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018 ]
    ORR was the percentage of participants with an objective response (complete response [CR] or partial response [PR]). Per RECIST (version 1.1), objective status of CR: target lesions and non-target diseases achieved CR, without new lesions; objective status of PR: target lesions achieved CR or PR while non-target diseases were non-CR/non-PD, indeterminate or missing, and without new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target diseases, CR: disappearance of all non-target lesions and normalization of tumor marker levels; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits; Indeterminate: progression had not been determined and >=1 non-target sites were not assessed or assessment methods were inconsistent with those used at baseline.
  • Percentage of Participants Achieving Disease Control (Disease Control Rate [DCR]) [ Time Frame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018 ]
    DCR was the percentage of participants achieving disease control (CR, PR or stable disease [SD] >=24 weeks from Cycle 1 Day 1 to PD or death due to any cause). The definitions for objective status of CR, PR, and PD per RECIST (version 1.1) can be found in the previous Outcome Measures. Per RECIST (version 1.1), objective status of SD: target lesions achieved SD (i.e., did not qualify for CR, PR or PD) while non-target diseases were assessed as non-CR/non-PD, indeterminate or missing, and there were no new lesions.
  • Duration of Response [ Time Frame: Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018 ]
    Duration of response was the time from first documentation of CR or PR to date of first documentation of PD or death for the participants with an objective response (CR or PR). The definitions of CR, PR, and PD per RECIST (version 1.1) can be found in the previous Outcome Measures.
  • 1-Year PFS Probability [ Time Frame: 1 year ]
    One-year PFS probability was defined as the probability (expressed as percentage) of PFS at 1 year after Cycle 1 Day 1.
  • Trough Plasma Concentration of Letrozole [ Time Frame: pre-dose of Cycle 1 Days 19, 20, 21 and Cycle 2 Day 1 ]
    Plasma samples were analyzed for letrozole concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric (HPLC/MS/MS) method.
  • Ratio Over Baseline for Skin Biomarker Phosphorylated Retinoblastoma Protein (pRb) Expression [ Time Frame: Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26 ]
    The pRb was one of the skin biomarkers and samples were assayed using immunohistochemistry (IHC) method. Ratio over baseline was calculated by dividing the H-score value for pRb at each specified time point by baseline value. The H-score value, which could range from 0 to 300 (strongest expression) with higher score representing stronger expression, was calculated from the total of each individual intensity of staining (0 [negative], 1+ [weak], 2+ [moderate], 3+ [strong]) multiplied by the percentages of cells (0 to 100) that represented that staining.
  • Ratio Over Baseline for Skin Biomarker Ki67 Expression [ Time Frame: Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26 ]
    The Ki67 was one of the skin biomarkers and samples were assayed using IHC method. Ratio over baseline was calculated by dividing the percentage of Ki67 positive cells at each specified time point by baseline value.
  • Ratio Over Baseline for Thymidine Kinase (TK) Concentration [ Time Frame: 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 ]
    Blood samples were collected to provide serum for the assessments of TK activity. The concentrations of TK were determined using enzyme-linked immunosorbent assay (ELISA) method. Ratio of serum TK concentration at each specified time point over baseline value was presented.
Original 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. ]
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 *

*   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 Unknown status
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 May 2019

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