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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington Identifier:
First received: July 26, 2006
Last updated: May 2, 2016
Last verified: May 2016
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.

Condition Intervention Phase
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
Biological: denileukin diftitox
Procedure: intraperitoneal administration
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other: flow cytometry
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Study of Intraperitoneal (I.P.) ONTAK® Administered to Patients With Advanced Stage Ovarian Cancer

Resource links provided by NLM:

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • MTD [ Time Frame: From baseline ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: April 2005
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Biological: denileukin diftitox
Given IP at 3 dose levels: 5mcg/kg of ONTAK, 15mcg/kg of ONTAK, or 25mcg/kg of ONTAK
Other Names:
  • DAB389 interleukin-2
  • DAB389 interleukin-2 immunotoxin
  • DAB389-IL2
  • DAB389IL-2
  • DAB389IL2
  • DABIL2
Procedure: 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
Other: laboratory biomarker analysis
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: flow cytometry
Correlative studies

Detailed 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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00357448

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Lupe Salazar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: University of Washington Identifier: NCT00357448     History of Changes
Obsolete Identifiers: NCT00268801
Other Study ID Numbers: 6193  NCI-2010-00832 
Study First Received: July 26, 2006
Last Updated: May 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Endometrial Neoplasms
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Cystic, Mucinous, and Serous
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Uterine Neoplasms
Denileukin diftitox processed this record on May 26, 2016