Overview

This trial is active, not recruiting.

Conditions neoplasms, breast neoplasms
Treatments pd-0332991, letrozole
Phase phase 2
Target CDK4
Sponsor Pfizer
Start date October 2012
End date March 2016
Trial size 58 participants
Trial identifier NCT01684215, A5481010

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Masking open label
Primary purpose treatment
Arm
(Experimental)
Phase 1 Part 1
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)
Phase 1 Part 2
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.
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)
Phase 2
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.
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.

Primary Outcomes

Measure
Number of participants with Dose-limiting toxicities (DLT)
time frame: Baseline up to 28 days
Investigator-assessed 1-year Progression Free Survival (PFS)
time frame: Baseline up to 52 weeks

Secondary Outcomes

Measure
Area under the Concentration-Time Curve (AUC)
time frame: 0, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Maximum Observed Plasma Concentration (Cmax)
time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose
Plasma Decay Half-Life (t1/2)
time frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose
Minimum Observed Plasma Trough Concentration (Cmin)
time frame: Day 15 of Cycle 1 and Cycle 2
Objective Response (OR)
time frame: Baseline up to 2.5 months
Disease Control (DC)
time frame: Baseline up to 2.5 years
Duration of Response (DR)
time frame: Baseline up to 2.5 months
Progression-Free Survival (PFS)
time frame: Baseline to measured progressive disease
Overall Survival (OS)
time frame: Baseline to date of death from any cause
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
Tumor tissue biomarkers
time frame: Baseline and End of the study

Eligibility Criteria

Male or female participants at least 20 years old.

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.

Additional Information

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