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

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

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

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