Overview

This trial is active, not recruiting.

Condition advanced breast cancer
Treatments palbociclib, letrozole
Phase phase 1
Target CDK4
Sponsor Pfizer
Start date September 2015
End date August 2017
Trial size 25 participants
Trial identifier NCT02499146, A5481019

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification pharmacokinetics study
Masking open label
Arm
(Experimental)
Combination therapy of palbociclib and letrozole
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
letrozole
2.5 mg , orally once daily (continuously)

Primary Outcomes

Measure
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Secondary Outcomes

Measure
Progression-Free Survival (PFS)
time frame: 2 years
QTc
time frame: 2 years
1-year PFS probability
time frame: 1 year
Disease Control
time frame: 2 years
Objective Response
time frame: 2 years
Duration of Response
time frame: 2 years
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
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
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.

Eligibility Criteria

Female participants from 18 years up to 65 years old.

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).

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Pfizer.