Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose of intraperitoneal
administration of ONTAK. SECONDARY OBJECTIVES: I. To evaluate the change in the number of
Tregs in the peritoneum with the administration of ONTAK. II. To evaluate the change in the
number of Tregs in the peripheral blood with the administration of ONTAK. III. To assess the
clinical impact of ONTAK on tumor burden by serial measurements of CA-125. IV. To assess the
level of circulating cytokines IL-2, IL-6, IL-10, TGF-beta2, and TNF-alpha in the peritoneum
and peripheral blood before and after I.P. ONTAK. OUTLINE: This is a dose escalation study.
Patients receive intraperitoneal denileukin diftitox over at least 15 minutes on days 1-3.
Treatment repeats every 14 days for 4 courses in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of denileukin
diftitox until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose-limiting toxicity. After the
completion of study treatment, patients are followed up at 1 and 2 weeks, monthly for 3
months, and then at 6 months.

Inclusion Criteria:

- Patients with a histologic diagnosis of epithelial ovarian carcinoma, primary
peritoneal carcinoma, or epithelial fallopian tube carcinoma

- Patients with the following histologic epithelial cell types are eligible: Serous
adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated
carcinoma, clear cell adenocarcinoma, transitional cell carcinoma, and mixed
epithelial carcinoma

- Patients with advanced stage refractory ovarian carcinoma: patients unable to achieve
first complete remission (CR) with first or second line chemotherapy OR patients with
disease relapse after achieving second CR

- Patients must be 30 days out from last chemotherapy; previous chemotherapy must
include a platinumbased regimen and paclitaxel (Taxol)

- Patients must have undergone primary debulking surgery

- Patients must have a peritoneal catheter suitable for I.P. infusion

- White blood cell count (WBC) > 3.0 THOU/ul

- Serum creatinine =< 2.5 mg/dL

- ALT =< 2.5 x upper limit of normal

- AST =< 2.5 x upper limit of normal

- Total bilirubin =< 2.0 x upper limit of normal

- Albumin >= 3.0 g/dL

- Subjects must have a Performance Status Score (Zubrod/SWOG Scale) =< 2

- Subjects must have recovered from major infections and/or surgical procedures and, in
the opinion of the investigator, not have a significant active concurrent medical
illness precluding protocol treatment

- Lymphocytes > 1.0 THOU/ul

- Platelets >= 100 THOU/ul

Exclusion Criteria:

- Prior treatment with ONTAK (DAB389IL-2) or DAB486IL-2

- Known history of hypersensitivity to diphtheria toxin or IL-2

- Moderate (symptomatic requiring the use of diuretics) or severe (symptomatic requiring
paracentesis or other invasive intervention) ascites

- Active autoimmune disease

- Known history of pulmonary disease except controlled asthma

- Known history significant cardiac disease

- Concurrent malignancy requiring active treatment

- Clinical or radiological evidence of acute bowel obstruction within 30 days of
enrollment