Brief Title
Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer
Official Title
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Safety and toxicity profile as assessed by the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events version 3.0
Secondary Outcome
Efficacy of ONTAK defined as a 25% reduction in the number of Tregs in either the peripheral blood and/or in the peritoneal cavity
Condition
Fallopian Tube Cancer
Intervention
denileukin diftitox
Study Arms / Comparison Groups
Arm I
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
11
Start Date
April 2005
Primary Completion Date
November 2009
Eligibility Criteria
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Lupe Salazar, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00357448
Organization ID
6193
Secondary IDs
NCI-2010-00832
Responsible Party
Sponsor
Study Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Lupe Salazar, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
May 2019