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

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT00357448

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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

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 Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Apr 1, 2005

Actual Primary Completion Date :

Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: ELISA Other: flow cytometry Correlative studies

Arm

Intervention/Treatment

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 Names:

ELISA

Other: flow cytometry

Correlative studies

Outcome Measures

Primary Outcome Measures

Safety and toxicity profile as assessed by the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events version 3.0 [From baseline]
MTD [From baseline]

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 [From baseline]
Clinical impact on course of disease as assessed by serum CA-125 measurements [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 [Pre- and post-treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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