Phase I trial to study the effectiveness of gene therapy in treating patients with ovarian
cancer that has not responded to previous treatment. Inserting the p53 gene into a person's
cancer cells may improve the body's ability to fight cancer or make the cancer cells more
sensitive to treatment.
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
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
- 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
- Nonmeasurable disease (with CA-125 at least 35)
- Ascites and/or pleural effusions allowed
- No borderline or low malignant potential tumors
- 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