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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Cancer

Treatments: Biological: recombinant interleukin-12

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003439

NCI-T97-0031

NCI-2012-02272

PCI-MWH-97-039

PCI-98-031

CDR0000066467 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Biological: recombinant interleukin-12