Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

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

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: 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

Relevance to patient case: not relevant