RATIONALE: Inserting the gene for p53 into a person's cancer cells may improve the body's
ability to fight cancer. Radiation therapy uses high-energy x-rays to damage tumor cells.
PURPOSE: Phase I trial to study the effectiveness of gene therapy plus radiation therapy in
treating patients who have non-small cell lung cancer.
- Determine the feasibility and tolerability of adenovirus p53 gene therapy and
radiotherapy in patients with non-small cell lung cancer with or without prior
radiotherapy to the indicator lesion(s).
- Determine p53 and p21 expression and induction of apoptosis and necrosis in patients
treated with this regimen.
- Assess any vector incorporation, antitumor response, local control, viral
dissemination, and development of adenovirus antibodies in patients treated with this
OUTLINE: This is a multicenter study. Patients are stratified by prior radiotherapy to the
indicator lesion(s) (yes vs no).
Adenovirus p53 is injected directly into an endobronchial lesion via bronchoscopy or into
locoregional tumors via multiple percutaneous punctures under fluoroscopic, ultrasonic, or
CT scan guidance on days 1, 3, and 8. Patients undergo radiotherapy beginning on day 2 and
continuing for a total of 10 days.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 1 year.
- Histologically proven non-small cell lung cancer with at least 1 lesion accessible
for endobronchial or percutaneous injection
- Measurable or evaluable disease
- Must have a requirement for palliative radiotherapy to the thorax
- Clinically stable enough to undergo 3 adenovirus injections
- 18 and over
- ECOG 0 or 1
- At least 12 weeks
- Platelet count greater than 100,000/mm^3
- PT and PTT normal
- Not specified
- No New York Heart Association class III or IV heart disease
- No active systemic viral, bacterial, or fungal infection requiring treatment
- No concurrent illness requiring hospitalization or IV medications or psychologic,
familial, sociologic, geographic, or other concurrent condition that would preclude
adequate follow up and compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
PRIOR CONCURRENT THERAPY:
- No prior adenoviral gene therapy
- Any number of any type of other prior biologic therapy allowed
- Any number of any type of prior chemotherapy allowed
- At least 2 weeks since prior systemic cancer therapy and no worse than grade 2
toxicity in any organ
- Any number of any type of prior endocrine therapy allowed
- See Disease Characteristics
- No prior radiotherapy greater than 50 Gy if prior and concurrent radiation fields
include the spinal cord
- No prior radiotherapy in fraction sizes greater than 2 Gy with the spinal cord in the
concurrent radiation field
- At least 4 weeks since surgical resection of lung tissue
- At least 2 weeks since any other prior surgery requiring general anesthesia and