Patient case: 64-year-old male with gastric cancer; genetic feature: ERBB2 amplification

Clinical trial: Iloprost in Preventing Lung Cancer in Patients at High Risk for This Disease

Summary: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Iloprost may be effective in preventing lung cancer.
  PURPOSE: This randomized phase II trial is studying how well iloprost works in preventing lung cancer in patients who are at high risk for this disease.

Detailed description: OBJECTIVES:
  Primary
  -  Compare the reversal of premalignant histological changes in the bronchial epithelium of patients at high risk for lung cancer (defined by > 20 pack years of smoking and sputum atypia) treated with iloprost vs placebo.
  -  Determine whether this drug modulates Ki-67 proliferation index (Antigen Ki-67) in these patients.
  -  Determine whether this drug affects prostaglandin metabolism in these patients.
  -  Determine the toxicity profile of this drug in these patients.
  Secondary
  -  Determine whether this drug modulates a panel of biomarkers, including MCM-2(Minichromosome maintenance protein: forms DNA helicase), EGFR (Epidermal growth factor receptor: cell surface receptor for the epidermal growth factor family of proteins. Mutations in EGFR expression or activity can result in cancer.) , HER2/neu (Human epidermal growth factor receptor 2 HER2 is a member of the EGFR family), RARβ (Retinoic Acic Receptor Beta is a nuclear transcription regulator and a member of the thyroid-steroid hormone receptor superfamily), p53, FHIT (Fragile histidine triad protein is an enzyme involved in purine metabolism and had been demonstrated to be a tumor suppressor), apoptotic index, and microvessel density, in these patients.
  -  Determine the genes whose expression is altered by this drug in these patients.
  OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to smoking status (current vs former) and participating center. Patients are randomized to 1 of 2 treatment arms.
  -  Arm I: Patients receive oral iloprost twice daily.
  -  Arm II: Patients receive oral placebo twice daily. In both arms, treatment continues for 6 months in the absence of unacceptable toxicity.
  Patients are followed at 1 month and then annually thereafter.
  PROJECTED ACCRUAL: A total of 152 patients (76 [38 current smokers and 38 former smokers] per treatment arm) will be accrued for this study within 2 years.

Eligibility: Inclusion Criteria:
  -  Current or former smoker with ≥ 20 pack-year history of smoking with no tobacco use within the past 6 months
  -  Mild atypia or worse on sputum cytology, or
  -  Bronchial biopsy with mild or worse dysplasia within the past 12 months
  -  Age 18 and over
  -  SWOG (Southwest Oncology Group)0-2
  -  Life expectancy at least 6 months
  -  Granulocyte count > 1,500/mm^3
  -  Platelet count > 100,000/mm^3
  -  Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
  -  Transaminases ≤ 2.5 times ULN
  -  Bilirubin ≤ 2.0 mg/dL
  -  Albumin ≥ 2.5 g/dL
  -  Creatinine ≤ 1.5 mg/dL
  -  Well-controlled atrial fibrillation OR rare (< 2 minutes) premature ventricular contractions allowed
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  Able and willing to undergo bronchoscopy
  Exclusion Criteria
  -  Clinically apparent bleeding diathesis
  -  Ventricular tachycardia
  -  Multifocal premature ventricular contractions or supraventricular tachycardias with rapid ventricular response
  -  Pneumonia or acute bronchitis within the past 2 weeks
  -  Hypoxemia (< 90% saturation with supplemental oxygen)
  -  Pregnant or nursing
  -  Malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  -  Serious medical condition that would preclude bronchoscopy or study participation
  -  Clinically active coronary artery disease
  -  Myocardial infarction within the past 6 weeks
  -  Chest pain
  -  Congestive heart failure
  -  Cardiac dysrhythmia that is potentially life-threatening
  Exclusion for PRIOR CONCURRENT THERAPY:
  -  Biologic therapy (Not specified)
  -  More than 5 years since prior chemotherapy
  -  More than 6 weeks since prior inhaled steroids
  -  More than 5 years since prior thoracic radiotherapy
  -  Surgery (Not specified)
  -  No prior prostacyclin

Relevance to patient case: not relevant