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A Study Of Oral Palbociclib (PD-0332991), A CDK4/6 Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-Line Treatment Of Postmenopausal Japanese Patients With ER (+) HER2 (-) Advanced Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01684215
First received: September 10, 2012
Last updated: June 12, 2017
Last verified: June 2017
  Purpose
This study is comprised of two portions: a Phase 1 portion and a Phase 2 portion. The Phase 1 portion is a single-country, non-randomized, open label, clinical trial which will evaluate the safety, tolerability, preliminary efficacy, and PK profile of PD-0332991 as a single agent in Japanese patients with advanced solid tumors, and PD-0332991 in combination with letrozole in the first-line treatment of Japanese patients with ER(+) HER2(-) ABC. The Phase 2 portion is a single-country, non-randomized, open-label, single-cohort, multi-center clinical trial to evaluate the efficacy and safety of PD-0332991 in combination with letrozole for the first-line treatment of postmenopausal Japanese patients with ER(+) HER2(-) ABC.

Condition Intervention Phase
Neoplasms Breast Neoplasms Drug: PD-0332991 Drug: letrozole Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study Of The Efficacy, Safety, And Pharmacokinetics Of Oral Pd-0332991, A Cyclin-dependent Kinase 4 And 6 (cdk4/6) Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-line Treatment Of Postmenopausal Japanese Patients With Er (+) Her2 (-) Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1 [ Time Frame: Lead-in period (Day -7) up to Day 28 (Cycle 1) ]
    DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [>]7 days); febrile neutropenia (grade greater than or equal to [>=]3 neutropenia,body temperature >=38.5 degree Celsius);grade >=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade >=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(>500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [<]50,000/microliter [mcL],absolute neutrophil count <1,000/mcL,hemoglobin <8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by >7 days;receipt of <75 percent of planned dose in first cycle due to toxicity.

  • Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1 [ Time Frame: Baseline (Day 1) up to 28 days after last dose of study drug (Day 677) ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious adverse events.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1 [ Time Frame: Baseline (Day 1) up to 28 days after last dose of study drug (Day 677) ]
    AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).

  • Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2 [ Time Frame: From initiation of treatment up to follow-up period (up to 12 months) ]
    PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.


Secondary Outcome Measures:
  • Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2 [ Time Frame: Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (Day 308), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (Day 677) ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious adverse events.

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2 [ Time Frame: Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (Day 308), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (Day 677) ]
    AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).

  • Number of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: Lead- in period (Day -7) up to end of treatment (Day 677) ]
    Abnormality criteria: hemoglobin: <0.8*lower limit of normal [LLN], platelets: <0.5*LLN or >1.75*upper limit of normal [ULN], leukocytes: <0.6*LLN or >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil,monocytes: >1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): >0.3*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN, total bilirubin, direct bilirubin: >1.5*ULN; blood urea nitrogen, creatinine: >1.3*ULN, uric acid: >1.2*ULN; sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium: <0.9*LLN or >1.1*ULN, phosphate: <0.8*LLN or >1.2*ULN; creatine kinase: >2.0*ULN, glucose fasting: <0.6*LLN or >1.5*ULN, glycosylated haemoglobin: >1.3*ULN;urinalysis dipstick (urine protein, urine blood >=1); urine protein 24 hour: >1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: >1.1*ULN.

  • Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [ Time Frame: Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

  • AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [ Time Frame: Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

  • Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7) ]
    AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.

  • AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7) ]
    AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

  • Area Under the Plasma Concentration-Time Curve From 0 to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7) ]
    AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

  • AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7) ]
    AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

  • Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7) ]
    AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.

  • AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7) ]
    AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

  • Apparent Oral Clearance of PD-0332991: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

  • Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.

  • Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.

  • Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [ Time Frame: Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.

  • Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

  • Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.

  • Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8 ]
    t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

  • Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1 [ Time Frame: Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7) ]
    Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

  • Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15 ]
    AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

  • Apparent Oral Clearance of PD-0332991: Phase 2 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

  • Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15 ]
    Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15 ]
    Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.

  • Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2 [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15 ]
    Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.

  • Percentage of Participants With Objective Response: Phase 1 [ Time Frame: From initiation of treatment up to disease progression (up to 30 months) ]
    Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]). PR was defined as a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.

  • Percentage of Participants With Objective Response: Phase 2 [ Time Frame: From initiation of treatment up to disease progression (up to 21 months) ]
    Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]). PR was defined as a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.

  • Duration of Response (DOR): Part 2 Phase 1 [ Time Frame: From initiation of treatment up to disease progression (up to 30 months) ]
    Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]) or PR (a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.

  • Duration of Response (DOR): Phase 2 [ Time Frame: From initiation of treatment up to disease progression (up to 21 months) ]
    Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]) or PR (a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.

  • Progression Free Survival (PFS): Part 2 Phase 1 [ Time Frame: From initiation of treatment up to disease progression (up to 30 months) ]
    PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  • Percentage of Participants With Disease Control (DC): Phase 2 [ Time Frame: From initiation of treatment up to disease progression (up to 21 months) ]
    Disease control was defined as CR, PR or stable disease for >=24 weeks according to the RECIST version 1.1 recorded in the time period between first dose of study treatment and disease progression or death to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]). PR was defined as >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Stable disease was defined as not achieving an objective response with confirmed CR or PR according to RECIST version 1.1, as determined by the investigators, relative to the response evaluable population, but remained stable for at least 24 weeks after first dose, then the best overall response for such a participant was considered as stable disease. Percentage of participants with disease control were reported.

  • Overall Survival (OS): Phase 2 [ Time Frame: From initiation of treatment up to follow-up period (up to 21 months) ]
    Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.

  • Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and End of Treatment [ Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, End of treatment (Day 677) ]
    The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.

  • Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and End of Treatment [ Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, End of treatment (Day 677) ]
    FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life. Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.

  • Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and End of Treatment [ Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, End of treatment (Day 677) ]
    FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of these 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.

  • Presence of Tumor Tissue Biomarker- Ki67: Phase 2 [ Time Frame: Baseline (Day 1) ]
    Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.

  • Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2 [ Time Frame: Baseline (Day 1) ]
    Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.


Enrollment: 61
Actual Study Start Date: October 19, 2012
Estimated Study Completion Date: June 28, 2018
Primary Completion Date: March 4, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-agent PD-0332991
Phase 1 Part 1
Drug: PD-0332991
PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
Experimental: PD-0332991 in combination with letrozole
Phase 1 Part 2
Drug: PD-0332991
PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
Drug: letrozole
Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.
Experimental: PD-0332991 with letrozole
Phase 2
Drug: PD-0332991
PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
Drug: letrozole
Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Phase 1

  • In Part 1, advanced solid tumor (except SCLC or retinoblastoma) proven histologically or cytologically at original diagnosis, that is refractory to standard therapy or for whom no standard of care therapy is available.
  • In Part 2 and Phase 2, post menopausal women with proven diagnosis of ER-positive, HER2-negative adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease (including bone only disease) not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
  • Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 or 1.
  • Resolved acute effects of any prior therapy to baseline severity or Grade ≤1

Phase 2

  • Adult women (≥ 20 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
  • Documentation of histologically or cytologically confirmed diagnosis of ER(+) breast cancer based on local laboratory results.
  • Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 to 2.

Exclusion Criteria:

Phase 1

  • Active uncontrolled or symptomatic CNS metastases.
  • Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse
  • Active or unstable cardiac disease or history of heart attack within 6 months

Phase 2

  • HER2 positive tumor based on local laboratory results utilizing one of the sponsor approved assays.
  • Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
  • Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684215

Locations
Japan
Aichi Cancer Center Hospital
Nagoya, Aichi, Japan, 464-8681
National Cancer Center Hospital East
Kashiwa, Chiba, Japan, 277-8577
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, Japan, 003-0804
Kumamoto Shinto General Hospital
Kumamoto-city, Kumamoto, Japan, 862-8655
Saitama Cancer Center
Kita-adachi-gun, Saitama, Japan, 362-0806
National Cancer Center Hospital
Chuo-Ku, Tokyo, Japan, 104-0045
Chiba Cancer Center
Chiba, Japan, 260-8717
National Hospital Organization Shikoku Cancer Center
Ehime, Japan, 791-0280
National Hospital Organization Kyushu Cancer Center
Fukuoka, Japan, 811-1395
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, Japan, 730-8518
Iwate Medical University Hospital
Iwate, Japan, 020-8505
Hakuaikai Medical Corporation Sagara Hospital
Kagoshima, Japan, 892-0833
Kumamoto University Hospital
Kumamoto, Japan, 860-8556
Kumamoto City Hospital
Kumamoto, Japan, 862-8505
Kyoto University Hospital
Kyoto, Japan, 606-8507
National Hospital Organization Osaka National Hospital
Osaka, Japan, 540-0006
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01684215     History of Changes
Other Study ID Numbers: A5481010
Study First Received: September 10, 2012
Results First Received: November 9, 2016
Last Updated: June 12, 2017

Keywords provided by Pfizer:
Phase 1/2
PD-0332991
palbociclib
Cyclin Dependent Kinase 4/6 inhibitor
Japanese
solid tumors
breast cancer
A5481010

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Letrozole
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on June 22, 2017