Gene Therapy in Treating Patients With Ovarian Cancer

OBJECTIVES:

I. Determine the maximum tolerated doses of adenovirus p53 in patients with platinum- and paclitaxel-resistant ovarian epithelial cancer.

II. Determine the qualitative and quantitative toxic effects of this regimen in these patients.

III. Document the observed anti-tumor activity of this regimen in these patients.

IV. Evaluate the biological endpoints (e.g., induction of apoptosis, p53 expression) of this regimen in these patients.

OUTLINE: This is a dose escalation study.

Patients undergo laparoscopy for p53 assessment and catheter placement. Patients receive daily intraperitoneal injections of adenovirus p53 (Ad-p53) for 5 days every 3 weeks. Treatment is repeated every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each are treated at each dose level of Ad-p53. The maximum tolerated dose is defined as the dose at which no more than 1 of 6 patients experiences dose limiting toxicity.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic ovarian epithelial cancer that is platinum- and paclitaxel resistant as defined by: Disease progression while on first-line regimen containing both a platinum drug and paclitaxel OR Tumor progression within 6 months of completion of platinum-based therapy (either as first- or second-line) or paclitaxel-based therapy (either as first- or second-line)
• Refractory or recurrent ovarian epithelial cancer as defined by: Lesions of any diameter
• Nonmeasurable disease (with CA-125 at least 35)
• Ascites and/or pleural effusions allowed
• No borderline or low malignant potential tumors

PATIENT CHARACTERISTICS:

• Age: 18 and over
• Performance status: Zubrod 0-2
• Life expectancy: At least 12 weeks
• WBC at least 3,000/mm3
• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Bilirubin no greater than 1.5 mg/dL PT/PTT normal
• Creatinine no greater than 1.4 mg/dL
• No active, unresolved upper respiratory infections
• Not HIV positive
• At least 5 years since prior malignancy, except nonmelanomatous skin cancer
• Willing and able to undergo placement of Tenckhoff catheter in the peritoneal cavity for sampling of ascites or peritoneal fluid
• No concurrent serious medical illness
• No untreated gastrointestinal obstruction
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• May have failed an unlimited number of prior chemotherapy regimens
• At least 30 days since prior chemotherapy
• No prior radiotherapy to the pelvis or abdomen
• Eligible for laparoscopy