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

Fallopian Tube Cancer Clinical Trial

Official title:

Phase I Dose Escalation Study of Intraperitoneal (I.P.) ONTAK® Administered to Patients With Advanced Stage Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00357448
• Other study ID #: 6193
• Secondary ID: NCI-2010-00832
• Status: Completed
• Phase: Phase 1
• Start date: April 2005

Study information

• Verified date: May 2019
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00268801

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Cystadenocarcinoma
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Clear Cell Cystadenocarcinoma
• Ovarian Endometrioid Adenocarcinoma
• Ovarian Mixed Epithelial Carcinoma
• Ovarian Mucinous Cystadenocarcinoma
• Ovarian Neoplasms
• Ovarian Serous Cystadenocarcinoma
• Ovarian Undifferentiated Adenocarcinoma
• Peritoneal Cavity Cancer
• Recurrent Ovarian Epithelial Cancer
• Stage III Ovarian Epithelial Cancer
• Stage IV Ovarian Epithelial Cancer

Intervention

Biological:
• denileukin diftitox
Given IP at 3 dose levels: 5mcg/kg of ONTAK, 15mcg/kg of ONTAK, or 25mcg/kg of ONTAK

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
• enzyme-linked immunosorbent assay
Correlative studies
• flow cytometry
Correlative studies

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and toxicity profile as assessed by the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events version 3.0		From baseline
Primary	MTD		From baseline
Secondary	Efficacy of ONTAK defined as a 25% reduction in the number of Tregs in either the peripheral blood and/or in the peritoneal cavity		From baseline
Secondary	Clinical impact on course of disease as assessed by serum CA-125 measurements		At baseline and at months 1, 2, 3, and 6
Secondary	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		Pre- and post-treatment