PV701 in Treating Patients With Advanced or Recurrent Peritoneal Cancer

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Completed

Phase 1

Conditions

Cancer

Treatments

Biological: PV701

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00055705

MSKCC-02080

NCI-1617

CDR0000270801

Details and patient eligibility

About

RATIONALE: PV701 may be able to kill tumor cells while leaving normal cells undamaged.

PURPOSE: Phase I trial to study the effectiveness of PV701 in treating patients who have advanced or recurrent ovarian epithelial, fallopian tube, primary peritoneal, colorectal, or other cancer found primarily within the peritoneal cavity.

Full description

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)