Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Gene Therapy in Treating Patients With Non-Small Cell Lung Cancer That Cannot Be Surgically Removed

Summary: RATIONALE: Exposing tumor cells to the p53 gene may improve the body's ability to fight non-small cell lung cancer.
  PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have non-small cell lung cancer that cannot be surgically removed.

Detailed description: OBJECTIVES:
  -  Evaluate the safety of multiple endobronchial treatments with adenovirus p53 bronchoalveolar lavage of a single lobe of the lung in patients with bronchoalveolar cell lung carcinoma.
  -  Evaluate expression of the p53 gene and induction of apoptosis in tumor and normal tissues exposed to the virus in these patients.
  -  Evaluate whether transbronchial administration of adenovirus p53 results in improved local tumor control in these patients.
  OUTLINE: This is a dose escalation study.
  Patients undergo biopsy and receive adenovirus p53 by bronchoalveolar lavage on days 1 and 15. Patients repeat biopsy on days 3 and 28. If there is evidence of clinical benefit or response without significant toxicity, patients may receive a maximum of 3 courses. Treatment beyond 3 courses must be approved by protocol investigator.
  Cohorts of 3 patients are treated at escalating dose levels of adenovirus p53. Patients in each cohort are followed for dose limiting toxicity (DLT) for 2 weeks after completion of one course before dose escalation proceeds in subsequent cohorts. If 1 of 3 patients at a dose level experiences dose limiting toxicity (DLT), then 2 additional patients are entered at the same dose level. If more than 1 of 5 patients experience DLT, the previous dose is the maximum tolerated dose (MTD). An additional 10 patients are treated at the MTD.
  Patients are followed every 3 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter.
  PROJECTED ACCRUAL: There will be 15 patients accrued into this study over 1 year.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed unresectable non-small cell lung cancer with a growth pattern allowing access to the majority of tumor cells via the airway (e.g., bronchioloalveolar or papillary adenocarcinoma)
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  ECOG 0-1
  Life expectancy:
  -  At least 12 weeks
  Hematopoietic:
  -  Platelet count greater than 100,000/mm^3
  -  Prothrombin time and partial thromboplastin time normal
  Hepatic:
  -  Bilirubin less than 1.5 mg/dL
  Renal:
  -  Creatinine less than 1.5 mg/dL
  Cardiovascular:
  -  No New York Heart Association class III or IV heart disease
  Pulmonary:
  -  Room air oxygen saturation greater than 90%
  -  FEV1 greater than 1.0 L pCO2 less than 50
  Other:
  -  HIV negative
  -  No active systemic viral, bacterial, or fungal infections requiring treatment
  -  No concurrent illness requiring hospitalization or intravenous medication
  -  Not pregnant or nursing
  -  Effective contraception required of all fertile patients
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  No prior adenovirus gene therapy
  -  At least 2 weeks since any systemic biologic therapy including prior biologic response modifiers and recovered
  Chemotherapy:
  -  At least 2 weeks since any prior systemic chemotherapy and recovered
  Endocrine therapy:
  -  Recovered from any prior endocrine therapy
  Radiotherapy:
  -  Recovered from any prior radiotherapy
  Surgery:
  -  At least 2 weeks since any surgical procedure requiring anesthesia
  -  At least 4 weeks since prior surgical resection of lung tissues
  Other:
  -  No other concurrent therapy

Relevance to patient case: not relevant