Cyclin Dependent Kinase (CDK)4/6 Inhibitor, PD0332991 in Advanced Non-small Cell Lung Cancer NSCLC.

Phase 2

Completed

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: PD0332991

• Registration Number: NCT01291017
• Lead Sponsor: University of Florida

Brief Summary

The purpose of this study is to determine the efficacy and the toxicities of the study drug PD0332991 in the treatment of patients with Stage IV non-small cell lung cancer with wildtype retinoblastoma protein (RB) and inactivated cyclin dependent kinase (CDK) N2A in the tumor.

Detailed Description

The oral drug PD0332991 is a highly selective reversible inhibitor of cyclin-dependent kinases 4 \& 6 that is being studied for use in the treatment of advanced non-small cell lung cancer.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-01
• Study First Submitted QC: 2011-02-04
• Study First Posted: 2011-02-07
• Primary Completion: 2014-02
• Study Completion: 2015-02
• Results First Submitted: 2015-03-12
• Results First Submitted QC: 2015-05-04
• Results First Posted: 2015-05-21
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-08
• Last Update Posted: 2016-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

• Histologically or cytologically proven non small cell lung cancer
• Stage IV (M1a or M1b) disease. Patients may also have recurrence of early-stage disease or locally advanced disease with the presence of new distant metastases.
• Cyclin dependent kinase (CDK)N2a (p16) protein absent or expressed at a low level in tumor biopsy specimen
• Failed or intolerant of at least one prior systemic chemotherapy regimen (there is no maximum number of prior chemotherapy regimens)
• Eastern cooperative oncology group (ECOG) performance status 0-2
• Age >18 years.
• Adequate organ and bone marrow function
• Measurable disease by standard RECIST v1.1 criteria
• Life expectancy of greater than 3 months

Exclusion Criteria

• Inability to understand or sign the informed consent document
• Inability or unwillingness to take oral medications
• No available tissue specimen for p16 analysis
• Chemotherapy or radiotherapy within 3 weeks prior to beginning the study drug
• Other investigational agents within 4 weeks prior to beginning the study drug
• All side effects from previous chemotherapy, radiotherapy or investigational agents not resolved, returned to baseline or returned to Grade 1 toxicity (exceptions are grade 2 alopecia and grade 2 peripheral neuropathy)
• Major surgery within 4 weeks prior to beginning the study drug
• Surgical scar from previous surgery not healed prior to beginning the study drug
• High-dose or chronic steroid use
• High-dose statins within 7 days
• History of rhabdomyolysis
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, stroke or myocardial infarction within 3 months, or psychiatric illness/social situations that would limit compliance with study requirements.
• Baseline corrected QT interval (QTc) >470ms
• Pre-existing clinically significant cardiac, hepatic or renal dysfunction at the discretion of the treating physician
• Untreated or uncontrolled (symptomatic or asymptomatic) brain metastases
• Leptomeningeal carcinomatosis
• Inability or unwillingness to use contraception during the treatment period by patients with reproductive potential.
• Pregnant or breastfeeding women
• HIV-positive patients on combination antiretroviral therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PD0332991	PD0332991	PD0332991 125 mg PO days 1 - 21

Primary Outcome Measures

Name	Time	Method
Tumor Response by Direct RECIST Measurement	6 months	Response is a decrease in the sum of the longest diameters of the target lesions by more than 30% compared to the baseline.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	14 months	Median overall survival
Progression-free Survival	12 months	Median progression-free survival.
Plasma Levels	6 months	Plasma levels of p16, phosphorylated RB and cyclin d1 in blood.
Grade of Study Drug Toxicity	24 months	The number of all toxicities and grades 3 and 4 (per CTCAE v3.0) toxicities that occured during the administration of the drug and during the follow up period.

Trial Locations

Locations (2)

UF Health Cancer Center; 🇺🇸 Gainesville, Florida, United States

H. Lee Moffitt Cancer and Research Institute; 🇺🇸 Tampa, Florida, United States