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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: PD0332991

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD0332991; PD0332991 125 mg PO days 1 - 21	Drug: PD0332991; PD0332991 125 mg PO days 1 - 21; Other Names: Palbociclib

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Priya Gopalan, MD, PhD, University of Florida

Publications and helpful links

Helpful Links

• UF Health Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 4, 2011
• First Posted (Estimate): February 7, 2011

Study Record Updates

• Last Update Posted (Estimate): May 13, 2016
• Last Update Submitted That Met QC Criteria: April 8, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Advanced stage
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: PD0332991