Interleukin-12 in Treating Patients With Ovarian Epithelial Cancer or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of intraperitoneal interleukin-12 in treating patients who have ovarian epithelial cancer or primary peritoneal cancer. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill tumor cells. Giving interleukin-12 directly into the peritoneal cavity may kill cancer cells

Detailed Description
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OBJECTIVES: I. Determine the response rate and progression-free interval in patients with peritoneal carcinomatosis associated with ovarian epithelial cancer or primary peritoneal carcinoma treated with intraperitoneal interleukin-12. II. Determine the qualitative and quantitative toxicity and reversibility of toxicity of this regimen in these patients. III. Determine peritoneal cavity tumor cell responses, in terms of negative cytology, conversion of aneuploidy to diploidy, and apoptosis as evidence of therapeutic effect, in patients treated with this regimen. IV. Assess quality of life in patients treated with this regimen. V. Determine the pharmacology and pharmacokinetics of this drug in these patients. VI. Determine whether this regimen facilitates adaptive or innate immunity in vivo or serum antibody responses to tumor-associated antigens in these patients. VII. Determine whether this regimen decreases expression of vascular endothelial growth factor, fibroblast growth factor 2, and interleukin-8 as surrogate markers of angiogenesis and whether a decrease in marker expression is associated with clinical activity of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive interleukin-12 intraperitoneally once weekly. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease receive 2 additional courses. Quality of life is assessed at baseline; prior to weeks 2, 4, 8, 12, and 16 of treatment; when patients are informed of their disease response; and then 2 weeks later. Patients are followed every 2 months for 1 year and then every 3 months for 1 year.

Official Title
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Phase II Study of Intraperitoneal Recombinant Human Interleukin-12 (rhIL-12) in Patients With Peritoneal Carcinomatosis (Residual Disease < 1cm) Associated With Ovarian Epithelial Cancer or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
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* Biological: recombinant interleukin-12


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed peritoneal carcinomatosis associated with ovarian epithelial or primary peritoneal epithelial carcinoma Surgically documented disease after prior platinum-based chemotherapy with or without surgery Minimal residual disease, defined as metastases less than 1 cm in largest diameter No significant adhesions or symptoms of obstruction No extra-abdominal or parenchymal disease No more than 6 weeks since prior primary chemotherapy Performance status - Zubrod 0-1 Absolute granulocyte count greater than 1,500/mm^3 Platelet count at least 100,000/mm^3 Lymphocyte count greater than 600/mm^3 Bilirubin no greater than 1.5 mg/dL SGOT or SGPT no greater than 2.5 times upper limit of normal Albumin at least 3.0 g/dL Hepatitis B and C negative Creatinine no greater than 1.5 mg/dL No significant cardiac disease No significant pulmonary disease No overt autoimmune disease No other malignancy within the past 10 years except squamous cell carcinoma in situ or basal cell skin cancer HIV negative Successful placement of peritoneal catheter No prior immunotherapy See Disease Characteristics Recovered from prior chemotherapy No concurrent chemotherapy No chronic steroid therapy No prior radiotherapy See Disease Characteristics Recovered from prior surgery At least 2 weeks since prior laparoscopy At least 4 weeks since prior laparotomy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (recombinant interleukin-12)<br>Patients receive interleukin-12 intraperitoneally once weekly. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease receive 2 additional courses. | Biological: recombinant interleukin-12<br>* Given intraperitoneally<br>* Other names: Ro 24-7472;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of remission determined by laparoscopy or laparotomy | Tested using an exact test for a single binomial proportion | Up to 2 years | 
| Toxicity graded using the NCI CTC version 3.0 | Evaluated for each dose level and each course of therapy. | Up to 2 years | 
| Progression-free interval |  | Up to 2 years |