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

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00357448

Purpose

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 I

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:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Interleukin-2 Denileukin diftitox

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

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

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357448

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Lupe Salazar

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

More Information

No publications provided

Responsible Party:	Salazar, Lupe, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00357448 History of Changes
Obsolete Identifiers:	NCT00268801
Other Study ID Numbers:	6193, NCI-2010-00832
Study First Received:	July 26, 2006
Last Updated:	November 15, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Adenocarcinoma
Carcinoma
Cystadenocarcinoma
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Endocrine Gland Neoplasms
Neoplasms by Site

Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Endometrial Neoplasms
Uterine Neoplasms
Denileukin diftitox

ClinicalTrials.gov processed this record on February 02, 2012