Interleukin-12 in Treating Patients With Refractory Advanced-Stage Ovarian Cancer or Abdominal Cancer

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of interleukin-12 in treating patients with refractory ovarian or abdominal cancers. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a persons's white blood cells to kill cancer cells.

Detailed Description
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OBJECTIVES: I. Assess the safety and maximum tolerated dose of recombinant human interleukin-12 (rhIL-12) administered by intraperitoneal infusion in patients with chemotherapy refractory advanced ovarian cancer and other diffuse abdominal carcinomatosis. II. Determine the immunopharmacologic profile of rhIL-12 in this patient population. III. Evaluate the biologic response in selected patients to rhIL-12 administered through intraperitoneal infusions. OUTLINE: This is a dose escalation, multicenter study. Cohorts of 3-6 patients each receive escalating doses of intraperitoneal recombinant human interleukin-12 (rhIL-12) administered weekly for 9 weeks. If a patient tolerates rhIL-12 and shows evidence of objective response or stable disease, patient may receive up to 9 additional weeks of treatment. Treatment continues in the absence of unacceptable toxicity or disease progression. Dose escalation continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which no more than 1 of 6 patients experiences dose limiting toxicity. All patients are followed for survival.

Official Title
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A Phase I Dose-Escalating Study of Recombinant Human Interleukin-12 (NSC # 672423) Administered by Intraperitoneal Infusion in Refractory Advanced Stage Ovarian Cancer and Other Abdominal Carcinomatosis

Conditions
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Cancer

Intervention / Treatment
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* Biological: recombinant interleukin-12


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed intraabdominal cancer Diffuse abdominal carcinomatosis Chemotherapy refractory advanced stage ovarian cancer Measurable disease Residual, recurrent, or metastatic disease beyond the scope of standard curative therapy Extension of disease to sites distant to the peritoneal cavity allowed Retroperitoneal lymphadenopathy allowed as long as there is evaluable intraabdominal disease No history of progressive brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Hemoglobin greater than 9 g/dL WBC greater than 3,000/mm3 Platelet count greater than 100,000/mm3 Bilirubin less than 2.0 mg/dL ALT less than 100 U/L Creatinine clearance greater than 60 mL/min Normal electrocardiogram No recent history of cardiac ischemia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Hepatitis B negative No evidence of clinical immunodeficiency syndromes or immunodeficiency associated diseases No history of autoimmune disease No concurrent major illness No serious infection requiring intravenous antibiotics No active peptic ulcer disease Must have free flow of fluid into the peritoneal space No leakage from the catheter exit site PRIOR CONCURRENT THERAPY: At least 3 weeks since prior biologic therapy (6 weeks for interleukin-2) No prior recombinant human interleukin-12 At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) No concurrent systemic chemotherapy No concurrent systemic corticosteroids No prior radiation therapy to the whole abdomen No concurrent radiotherapy At least 3 weeks since prior exposure to any investigational drug No concurrent investigational drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Arm I<br>Cohorts of 3-6 patients each receive escalating doses of intraperitoneal recombinant human interleukin-12 (rhIL-12) administered weekly for 9 weeks. If a patient tolerates rhIL-12 and shows evidence of objective response or stable disease, patient may receive up to 9 additional weeks of treatment. Treatment continues in the absence of unacceptable toxicity or disease progression. Dose escalation continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which no more than 1 of 6 patients experiences dose limiting toxicity. | Biological: recombinant interleukin-12<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV gastric cancer, recurrent gastric cancer, recurrent pancreatic cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, stage IV anal cancer, recurrent anal cancer, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer, metastatic gastrointestinal carcinoid tumor, recurrent gastrointestinal carcinoid tumor, advanced adult primary liver cancer, recurrent adult primary liver cancer, stage IV endometrial carcinoma, recurrent endometrial carcinoma, small intestine adenocarcinoma, unresectable gallbladder cancer, recurrent gallbladder cancer, unresectable extrahepatic bile duct cancer, recurrent extrahepatic bile duct cancer, recurrent small intestine cancer, stage IV prostate cancer, recurrent prostate cancer, fallopian tube cancer, primary peritoneal cavity cancer, stage IV pancreatic cancer