This trial is active, not recruiting.

Conditions fallopian tube cancer, ovarian clear cell cystadenocarcinoma, ovarian endometrioid adenocarcinoma, ovarian mixed epithelial carcinoma, ovarian mucinous cystadenocarcinoma, ovarian serous cystadenocarcinoma, ovarian undifferentiated adenocarcinoma, peritoneal cavity cancer, recurrent ovarian epithelial cancer, stage iii ovarian epithelial cancer, stage iv ovarian epithelial cancer
Treatments denileukin diftitox, intraperitoneal administration, laboratory biomarker analysis, enzyme-linked immunosorbent assay, flow cytometry
Phase phase 1
Sponsor University of Washington
Collaborator National Cancer Institute (NCI)
Start date April 2005
End date November 2009
Trial size 11 participants
Trial identifier NCT00357448, 6193, NCI-2010-00832, NCT00268801


RATIONALE: Biological therapies, such as denileukin difitox, may stimulate the immune system in different ways and may prevent tumor cells from growing. PURPOSE: This phase I trial is studying the side effects and best dose of denileukin diftitox in treating patients with advanced refractory ovarian cancer, primary peritoneal carcinoma, or epithelial fallopian tube cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.
denileukin diftitox DAB389 interleukin-2
Given IP at 3 dose levels: 5mcg/kg of ONTAK, 15mcg/kg of ONTAK, or 25mcg/kg of ONTAK
intraperitoneal administration
After completion of I.P. normal saline infusion, the I.P. catheter will be capped and patients will be turned/rotated for 1 hour to help facilitate I.P. bathing w/ONTAK; patients will be turned/rotated every 15 minutes in 4 different positions for a total of 1 hour
laboratory biomarker analysis
Correlative studies
enzyme-linked immunosorbent assay ELISA
Correlative studies
flow cytometry
Correlative studies

Primary Outcomes

Safety and toxicity profile as assessed by the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events version 3.0
time frame: From baseline
time frame: From baseline

Secondary Outcomes

Efficacy of ONTAK defined as a 25% reduction in the number of Tregs in either the peripheral blood and/or in the peritoneal cavity
time frame: From baseline
Clinical impact on course of disease as assessed by serum CA-125 measurements
time frame: At baseline and at months 1, 2, 3, and 6
Changes in circulating cytokines IL-2, IL-6, IL-10, TGF-beta2, and TNF-alpha in the peripheral blood and at the site of disease as measured by ELISA
time frame: Pre- and post-treatment

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

Official title Phase I Dose Escalation Study of Intraperitoneal (I.P.) ONTAK® Administered to Patients With Advanced Stage Ovarian Cancer
Principal investigator Lupe Salazar
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by University of Washington.