PV701 in Treating Patients With Advanced or Recurrent Peritoneal Cancer

OBJECTIVES:

• Determine the dose-limiting toxicity and maximum tolerated dose of intraperitoneal PV701 after desensitization in patients with advanced or recurrent malignancy largely confined to the peritoneal cavity these patients.
• Determine the optimal desensitization dose of intravenous PV701 in these patients.
• Determine the safety of this drug, in terms of cumulative toxicity, in these patients.
• Determine, preliminarily, the antitumor activity of this drug in these patients.
• Determine the presence and duration of viral shedding, viremia, and immunogenicity of this drug.

OUTLINE: This is an open-label, dose-escalation study comprising 2 different treatment schedules.

• Schedule I (optimal desensitization dose): Patients receive PV701 IV over 30 minutes on day 1 followed by intraperitoneal (IP) PV701 on days 4, 7, and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PV701 IV and IP until the optimal desensitization dose (ODD) is determined. The ODD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity (DLT).

• Schedule II (maximum tolerated dose):Patients receive the same regimen as in schedule I using PV701 IV at the ODD.

Cohorts of 3-6 patients receive escalating doses of PV701 IP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.

PROJECTED ACCRUAL: A total of 3-50 patients will be accrued for this study within 10-17 months.

DISEASE CHARACTERISTICS:

• Histological confirmation of 1 of the following:

• Ovarian epithelial carcinoma
• Fallopian tube cancer
• Primary peritoneal cancer
• Advanced colorectal carcinoma
• Other malignancy confined to the peritoneal cavity or peritoneal surfaces
• No lesion greater than 2 cm in greatest diameter based on surgical re-assessment
• Low burden of tumor in the abdominal or pelvic cavities and no clinically significant ascites
• Received potentially effective therapy when available (e.g., platinum/taxane for ovarian cancer, fluoropyrimidine-based therapy for colorectal cancer)
• No concurrent hematological malignancy (e.g., chronic lymphocytic leukemia or non-Hodgkin's lymphoma)
• No bilateral adrenal metastases
• No adrenal metastases in the remaining adrenal gland after adrenalectomy (including radical nephrectomy)
• No lung tumors 5 cm or more
• No pleural effusions (at least 25% of hemithorax) by radiography
• No CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 1.5 times ULN
• No uncontrolled hepatic dysfunction
• No active hepatitis B or C

Renal

• See Disease Characteristics
• Creatinine no greater than 1.6 mg/dL AND/OR
• Creatinine clearance at least 50 mL/min
• No uncontrolled renal dysfunction

Cardiovascular

• No uncontrolled cardiovascular dysfunction
• No myocardial infarction within the past 6 months
• No life-threatening arrhythmias within the past 6 months

Pulmonary

• See Disease Characteristics
• No uncontrolled pulmonary dysfunction
• No pulmonary atelectasis (lobar)
• No pulmonary infiltrates (lobar)
• No pulmonary consolidation (lobar or segmental)
• No baseline grade II dyspnea

Adrenal

• See Disease Characteristics
• No uncontrolled adrenal dysfunction
• No known adrenal insufficiency

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled gastrointestinal dysfunction
• No neurological dysfunction
• No serious medical or psychological condition that would preclude study participation or increase the risk of adverse effects of the study treatment
• No history of serious immunodeficiency
• No active uncontrolled bacterial infection (including asymptomatic urinary tract infection)
• No contraindication to intraperitoneal therapy including the following:

• Intra-abdominal infection
• Dense widespread adhesions
• Peritonitis
• Periumbilical infection
• Bowel obstruction
• Ileostomy
• No hypersensitivity to eggs
• No continued contact with live birds (e.g., poultry farmers, veterinarians, laboratory technicians, pet store owners, breeders)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No more than 3 prior cytotoxic chemotherapy regimens
• More than 30 days since prior chemotherapy

Endocrine therapy

• More than 14 days since prior systemic corticosteroids

Radiotherapy

• More than 30 days since prior radiotherapy

Surgery

• See Disease Characteristics
• No prior complete or partial lobectomy with removal of lung tissue at least segmental size
• No prior organ allograft

Other

• Recovered from prior therapy
• More than 14 days since prior antiviral medication
• More than 4 weeks since prior immunosuppressive drugs
• No other concurrent investigational drugs
• No concurrent chronic immunosuppressive drugs (e.g., cyclosporine)
• No vaccination for influenza within 48 hours of study drug administration
• No concurrent hypoglycemic agents
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy