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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

denileukin diftitox

intraperitoneal administration

laboratory biomarker analysis

enzyme-linked immunosorbent assay

flow cytometry

About this trial

This is an interventional treatment trial for Fallopian Tube Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm 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.

Outcomes

Primary Outcome Measures

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

MTD

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

Clinical impact on course of disease as assessed by serum CA-125 measurements

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

Full Information

NCT ID

NCT00357448

First Posted

July 26, 2006

Last Updated

May 13, 2019

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00357448

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

April 2005 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I

Arm Type

Experimental

Arm 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.

Intervention Type

Biological

Intervention Name(s)

denileukin diftitox

Other Intervention Name(s)

DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DAB389IL-2, DAB389IL2, DABIL2

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

intraperitoneal administration

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

enzyme-linked immunosorbent assay

Other Intervention Name(s)

ELISA

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

flow cytometry

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

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

Title

MTD

Time Frame

From baseline

Secondary Outcome Measure Information:

Title

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

Title

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

Title

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lupe Salazar

Organizational Affiliation

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Fallopian Tube Cancer, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial