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

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ClinicalTrials.gov Identifier: NCT00357448
Recruitment Status : Completed
First Posted : July 27, 2006
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE July 26, 2006
First Posted Date  ICMJE July 27, 2006
Last Update Posted Date May 14, 2019
Study Start Date  ICMJE April 2005
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2010)
  • 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 ]
  • MTD [ Time Frame: From baseline ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00357448 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2010)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer
Official Title  ICMJE Phase I Dose Escalation Study of Intraperitoneal (I.P.) ONTAK® Administered to Patients With Advanced Stage Ovarian Cancer
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Biological: denileukin diftitox
  • Procedure: intraperitoneal administration
  • Other: laboratory biomarker analysis
  • Other: enzyme-linked immunosorbent assay
  • Other: flow cytometry
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 13, 2010)
11
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00357448
Other Study ID Numbers  ICMJE 6193
NCI-2010-00832
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Lupe Salazar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP