NCT00357448

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
11

participants targeted

Target at below P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2005

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

July 26, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 27, 2006

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2009

Completed
Last Updated

May 14, 2019

Status Verified

May 1, 2019

Enrollment Period

4.6 years

First QC Date

July 26, 2006

Last Update Submit

May 13, 2019

Conditions

Fallopian Tube CancerOvarian Clear Cell CystadenocarcinomaOvarian Endometrioid AdenocarcinomaOvarian Mixed Epithelial CarcinomaOvarian Mucinous CystadenocarcinomaOvarian Serous CystadenocarcinomaOvarian Undifferentiated AdenocarcinomaPeritoneal Cavity CancerRecurrent Ovarian Epithelial CancerStage III Ovarian Epithelial CancerStage IV Ovarian Epithelial Cancer

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (3)

  • 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

Study Arms (1)

Arm I

EXPERIMENTAL

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 diftitoxProcedure: intraperitoneal administrationOther: laboratory biomarker analysisOther: enzyme-linked immunosorbent assayOther: flow cytometry

Interventions

denileukin diftitoxBIOLOGICAL

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

Also known as: DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DAB389IL-2, DAB389IL2, DABIL2
Arm I
intraperitoneal administrationPROCEDURE

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

Arm I
laboratory biomarker analysisOTHER

Correlative studies

Arm I
enzyme-linked immunosorbent assayOTHER

Correlative studies

Also known as: ELISA
Arm I
flow cytometryOTHER

Correlative studies

Arm I

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +1 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

  • Liao JB, Jejurikar NS, Hitchcock-Bernhardt KM, Gwin WR, Reichow JL, Dang Y, Childs JS, Coveler AL, Swensen RE, Goff BA, Disis ML, Salazar LG. Intraperitoneal immunotherapy with denileukin diftitox (ONTAK) in recurrent refractory ovarian cancer. Gynecol Oncol. 2024 Dec;191:74-79. doi: 10.1016/j.ygyno.2024.09.019. Epub 2024 Oct 2.

    PMID: 39362046DERIVED

MeSH Terms

Conditions

Fallopian Tube NeoplasmsCarcinoma, Ovarian Epithelial

Interventions

denileukin diftitoxInjections, IntraperitonealEnzyme-Linked Immunosorbent AssayFlow Cytometry

Condition Hierarchy (Ancestors)

Genital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFallopian Tube DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeOvarian NeoplasmsEndocrine Gland NeoplasmsOvarian DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

InjectionsDrug Administration RoutesDrug TherapyTherapeuticsImmunoenzyme TechniquesImmunoassayImmunologic TechniquesInvestigative TechniquesImmunosorbent TechniquesImmunohistochemistryMolecular Probe TechniquesCell SeparationCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisCytophotometryFluorometryLuminescent MeasurementsPhotometryChemistry Techniques, Analytical

Study Officials

  • Lupe Salazar

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 26, 2006

First Posted

July 27, 2006

Study Start

April 1, 2005

Primary Completion

November 1, 2009

Last Updated

May 14, 2019

Record last verified: 2019-05

Locations

US(1)