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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Clinical Trail of the Cyclin Dependent Kinase (CDK)4/6 Inhibitor, PD0332991 in Previously Treated, Advanced NSCLC Patients With Wildtype Retinoblastoma Protein (RB) and Inactive Cyclin Dependent Kinase (CDK)N2a

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: PD0332991


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD0332991<br>PD0332991 125 mg PO days 1 - 21 | Drug: PD0332991<br>* PD0332991 125 mg PO days 1 - 21<br>* Other names: Palbociclib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response by Direct RECIST Measurement | Response is a decrease in the sum of the longest diameters of the target lesions by more than 30% compared to the baseline. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Median overall survival | 14 months | 
| Progression-free Survival | Median progression-free survival. | 12 months | 
| Plasma Levels | Plasma levels of p16, phosphorylated RB and cyclin d1 in blood. | 6 months | 
| Grade of Study Drug Toxicity | 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. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced stage