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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01291017
• Other study ID #: PD0332991
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 1, 2011
• Last updated: January 11, 2016
• Start date: February 2011
• Est. completion date: March 2016

Study information

• Verified date: January 2016
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: March 2016
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-small Cell Lung Cancer

Intervention

Drug:
• PD0332991
PD0332991 125 mg PO days 1 - 21

Locations

Country	Name	City	State
United States	UF Health Cancer Center	Gainesville	Florida
United States	H. Lee Moffitt Cancer and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Overall Survival	Median overall survival	14 months	No
Secondary	Progression-free Survival	Median progression-free survival.	12 months	No
Secondary	Plasma Levels	Plasma levels of p16, phosphorylated RB and cyclin d1 in blood.	6 months	No
Secondary	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	Yes

External Links

•   UF Health Cancer Center