Gene Therapy in Treating Patients With Non-small Cell Lung Cancer That Cannot Be Surgically Removed

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 1

Conditions: Lung Cancer

Treatments: Biological: Ad5CMV-p53 gene

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00003649

CDR0000066741

E-6597

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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