Clinical trial NCT01291017: Cyclin Dependent Kinase (CDK)4/6 Inhibitor, PD0332991 in Advanced Non-small Cell Lung Cancer NSCLC.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Advanced stage
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2011-02-07
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor Response by Direct RECIST Measurement
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival
timeFrame: 14 months
measure: Progression-free Survival
timeFrame: 12 months
measure: Plasma Levels
timeFrame: 6 months
measure: Grade of Study Drug Toxicity
timeFrame: 24 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Health Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer and Research Institute
state: Florida
Study officials:
affiliation: University of Florida
name: Priya Gopalan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: