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 currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01684215
First received: September 10, 2012
Last updated: July 8, 2014
Last verified: July 2014
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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) [ Time Frame: Baseline up to 28 days ] [ Designated as safety issue: Yes ]
    Number of participants with Dose-limiting toxicities (DLT)

  • Investigator-assessed 1-year Progression Free Survival (PFS) [ Time Frame: Baseline up to 52 weeks ] [ Designated as safety issue: No ]
    PFS at 12 months after first dose of study treatment


Secondary Outcome Measures:
  • Area under the Concentration-Time Curve (AUC) [ Time Frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ] [ Designated as safety issue: No ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose ] [ Designated as safety issue: No ]
    Maximum Observed Plasma Concentration (Cmax)

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose ] [ Designated as safety issue: No ]
    Time to Reach Maximum Observed Plasma Concentration (Tmax)

  • Plasma Decay Half-Life (t1/2) [ Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Day 15 of Cycle 1 and Cycle 2 ] [ Designated as safety issue: No ]
    Minimum Observed Plasma Trough Concentration (Cmin)

  • Objective Response (OR) [ Time Frame: Baseline up to 2.5 months ] [ Designated as safety issue: No ]
    OR is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1. recorded from randomization until disease progression or death due to any cause.

  • Disease Control (DC) [ Time Frame: Baseline up to 2.5 years ] [ Designated as safety issue: No ]
    DC is defined as complete response (CR), partial response (PR), or stable disease (SD) =24 weeks according to the RECIST version 1.1 recorded in the time period between randomization and disease progression or death to any cause.

  • Duration of Response (DR) [ Time Frame: Baseline up to 2.5 months ] [ Designated as safety issue: No ]
    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer.

  • Progression-Free Survival (PFS) [ Time Frame: Baseline to measured progressive disease ] [ Designated as safety issue: No ]
    Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

  • Overall Survival (OS) [ Time Frame: Baseline to date of death from any cause ] [ Designated as safety issue: No ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

  • Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) [ Time Frame: Cycles 1, 2 and 3 and then every other cycle thereafter starting with Cycle 5 ] [ Designated as safety issue: No ]
    FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer.

  • Tumor tissue biomarkers [ Time Frame: Baseline and End of the study ] [ Designated as safety issue: No ]
    Tumor tissue biomarkers will be analyzed to investigate possible associations with resistance/sensitivity to treatment with study drugs. Biomarkers that will be analyzed will be selected based on their known relevance to mechanisms involved in cell cycle regulation.


Estimated Enrollment: 58
Study Start Date: October 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: March 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 once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. 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
Genders Eligible for Study:   Both
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

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

Locations
Japan
Pfizer Investigational Site Active, not recruiting
Kashiwa, Chiba, Japan
Pfizer Investigational Site Not yet recruiting
Sapporo, Hokkaido, Japan
Pfizer Investigational Site Not yet recruiting
Kita-adachi-gun, Saitama, Japan
Pfizer Investigational Site Active, not recruiting
Chuo-Ku, Tokyo, Japan
Pfizer Investigational Site Not yet recruiting
Chiba, Japan
Pfizer Investigational Site Not yet recruiting
Ehime, Japan
Pfizer Investigational Site Recruiting
Fukuoka, Japan
Pfizer Investigational Site Not yet recruiting
Hiroshima, Japan
Pfizer Investigational Site Not yet recruiting
Kagoshima, Japan
Pfizer Investigational Site Not yet recruiting
Kumamoto, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01684215     History of Changes
Other Study ID Numbers: A5481010
Study First Received: September 10, 2012
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014