Clinical trial NCT00003439: Interleukin-12 in Treating Patients With Refractory Advanced-Stage Ovarian Cancer or Abdominal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-05-20
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Robert P. Edwards, MD
role: STUDY_CHAIR
References: