Back to results

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

Primary Purpose

Advanced Breast Cancer

Status

Active

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Palbociclib

Letrozole

About this trial

This is an interventional other trial for Advanced Breast Cancer focused on measuring Palbociclib, PD-0332991, pharmacokinetics, breast cancer patients, Chinese

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

Beijing Cancer Hospital/Oncology department
Sun Yat-Sen University Cancer Center
Guangdong General Hospital/Department of Breast Surgery
Harbin Medical University Cancer Hospital
The first hospital of jilin university
The First Affiliated Hospital of College of Medicine, Zhejiang University
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cohort 1

Arm Description

Combination therapy of palbociclib and letrozole

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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).

Secondary Outcome Measures

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

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

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

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

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)

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])

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])

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

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

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

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

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

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

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.

Full Information

NCT ID

NCT02499146

First Posted

July 13, 2015

Last Updated

June 23, 2022

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT02499146

Brief Title

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

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 11, 2015 (Actual)

Primary Completion Date

July 31, 2018 (Actual)

Study Completion Date

January 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Breast Cancer

Keywords

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Combination therapy of palbociclib and letrozole

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Letrozole

Intervention Description

2.5 mg , orally once daily (continuously)

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

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

Title

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

Description

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

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

Title

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

Description

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

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

Title

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

Description

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

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

Title

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

Description

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.

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

Title

Multiple-dose PK: Vz/F for Palbociclib

Description

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

Title

Multiple-dose PK: t1/2 for Palbociclib

Description

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

Title

Multiple-dose PK: CL/F for Palbociclib

Description

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.

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

Title

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

Description

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

Title

Observed Accumulation Ratio (Rac) for Palbociclib

Description

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).

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

Title

Steady State Accumulation Ratio (Rss) for Palbociclib

Description

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).

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

Secondary Outcome Measure Information:

Title

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

Description

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)

Title

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

Description

Time Frame

up to 2.8 years by primary completion date of 31 July 2018

Title

Number of Participants With Laboratory Test Abnormalities

Description

Time Frame

up to 2.8 years by primary completion date of 31 July 2018

Title

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

Description

Time Frame

up to 2.8 years by primary completion date of 31 July 2018

Title

Progression-Free Survival (PFS)

Description

Time Frame

Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018

Title

Percentage of Participants Achieving Objective Response (Objective Response Rate [ORR])

Description

Time Frame

Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018

Title

Percentage of Participants Achieving Disease Control (Disease Control Rate [DCR])

Description

Time Frame

Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018

Title

Duration of Response

Description

Time Frame

Every 12 weeks from Cycle 1 Day 1, up to 144 weeks by primary completion date of 31 July 2018

Title

1-Year PFS Probability

Description

One-year PFS probability was defined as the probability (expressed as percentage) of PFS at 1 year after Cycle 1 Day 1.

Time Frame

1 year

Title

Trough Plasma Concentration of Letrozole

Description

Plasma samples were analyzed for letrozole concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric (HPLC/MS/MS) method.

Time Frame

pre-dose of Cycle 1 Days 19, 20, 21 and Cycle 2 Day 1

Title

Ratio Over Baseline for Skin Biomarker Phosphorylated Retinoblastoma Protein (pRb) Expression

Description

Time Frame

Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26

Title

Ratio Over Baseline for Skin Biomarker Ki67 Expression

Description

Time Frame

Baseline (Day -1), lead-in phase Days 1 and 2, Cycle 1 Days 21, 22, 23, 24, 25, 26

Title

Ratio Over Baseline for Thymidine Kinase (TK) Concentration

Description

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

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Beijing Cancer Hospital/Oncology department

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100142

Country

China

Facility Name

Sun Yat-Sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Facility Name

Guangdong General Hospital/Department of Breast Surgery

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Facility Name

Harbin Medical University Cancer Hospital

City

Harbin

State/Province

Heilongjiang

ZIP/Postal Code

150081

Country

China

Facility Name

The first hospital of jilin university

City

Changchun

State/Province

Jilin

ZIP/Postal Code

130021

Country

China

Facility Name

The First Affiliated Hospital of College of Medicine, Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310003

Country

China

Facility Name

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

City

Beijing

ZIP/Postal Code

100021

Country

China

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing 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.

Citations:

PubMed Identifier

34554584

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.

Results Reference

derived

PubMed Identifier

33835229

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.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A5481019&StudyName=Palbociclib%20%28PD-0332991%29%20Pharmacokintetics%20Study%20In%20Postmenopausal%20Chinese%20Women%20With%20ER%20%28+%29%2C%20HER2%20%28-%29%20Advanced%20Breast%20Cancer%20

Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs