ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment

November 9, 2018 updated by: Mary (Nora) Disis, University of Washington

Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer

RATIONALE: ONTAK may be able to help reduce the type of cells that prevent other types of immune cells from attacking the breast cancer cells.

PURPOSE: This phase I/II trial is studying the safety of ONTAK and its possible side effects to see how well it works in treating patients with advanced breast cancer that did not respond to previous treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety of ONTAK infusion in patients with advanced refractory breast cancer.

II. To evaluate the effect of ONTAK administration on peripheral blood T-regulatory cells.

SECONDARY OBJECTIVES:

I. To evaluate the incidence of IL-2R expression in tumor samples and investigate the correlation of tumor IL-2R expression and tumor response to ONTAK therapy.

II. To evaluate levels of circulating sIL-2R before and after ONTAK therapy. III. To evaluate the effect of ONTAK on endogenous tumor specific immunity. IV. To evaluate the potential anti-tumor effects of ONTAK in patients with advanced refractory breast cancer.

OUTLINE:

Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with advanced stage refractory breast cancer
  • Progressive or relapsed disease following standard therapy
  • Patients must have measurable disease that can include, but is not limited to bone; specifically, patients must have measurable extraskeletal disease that can be accurately measured in at least one dimension as >= 20 mm with conventional CT techniques or >= 10 mm with spiral CT scan; measurable (bi-dimensional) chest wall disease will also be allowed
  • Patients must be at least 14 days out from last cytotoxic chemotherapy; patients on bisphosphonates are eligible
  • White blood cell count (WBC) > 3.0 THOU/ul
  • ANC > 1.0 THOU/ul
  • Platelets >= 100 THOU/ul
  • Serum creatinine =< 2.0 mg/dL or creatinine clearance (calculated) >= 60 ml/min
  • ALT/AST =< 2.0 x upper limit of normal
  • Total bilirubin =< 1.5 x upper limit of normal
  • Albumin >= 3.0 g/dL
  • Subjects must have a Performance Status Score (ECOG 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
  • Men and women of reproductive ability must agree to contraceptive use during the study and for 1month after ONTAK treatment is discontinued

Exclusion Criteria:

  • Prior treatment with ONTAK (DAB389 IL-2) or DAB486 IL-2
  • Known history of hypersensitivity to diphtheria toxin or IL-2
  • Active autoimmune disease
  • Known history of pulmonary disease except controlled asthma
  • History of or pre-existing, cardiovascular disease as defined by New York Heart Association (NYHA) Class III-IV categorization
  • Pregnant or breast-feeding women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I
Patients receive ONTAK IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
  • immunohistochemistry
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Names:
  • ELISA
Genetic: protein expression analysis
Correlative studies
Biological: ONTAK
Given IV
Other Names:
  • DAB389 interleukin-2
  • DAB389 interleukin-2 immunotoxin
  • DAB389-IL2
  • DAB389IL-2
  • denileukin diftitox
  • DAB389IL2
  • DABIL2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
Time Frame: 7 Days after last dose of ONTAK
Subjects are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, serum albumin, complete blood counts, symptom assessment, and physical exams performed at every cycle until 3 weeks after the final dose of ONTAK. All adverse events for all systems are graded on a scale of 1-5 using CTCAE v3.0.
7 Days after last dose of ONTAK
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
Time Frame: 21 days after cycle 6
The efficacy of ONTAK in depleting Tregs will be defined as a decrease in peripheral blood Tregs by 25% of each individual subject's baseline. All subjects will undergo blood draws at baseline and post ONTAK infusions at designated time points. Tregs from the peripheral blood will be quantitated using flow cytometry.
21 days after cycle 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
Time Frame: 21 days after cycle 6
The incidence of IL-2 expression and its receptor complex, IL-2R in tumor samples will be evaluated by IHC analysis. Tumor sections will be interpreted as either positive or negative.
21 days after cycle 6
Presence of Circulating sIL-2R in the Peripheral Blood
Time Frame: 21 days after cycle 6
Evaluate levels of circulating sIL-2R (pg/ml) in the peripheral blood assessed before and after ONTAK therapy. Changes from baseline will be tabulated.
21 days after cycle 6
Presence of Endogenous Tumor-specific Immunity
Time Frame: 21 days after cycle 6
Evaluate the effect of ONTAK on endogenous tumor specific immunity
21 days after cycle 6
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Time Frame: 21 days after cycle 6
Anti-tumor effects of ONTAK will be determined by evaluating tumor response and progression per RECIST. An objective response to ONTAK will be defined as achieving a CR or PR. Analysis of the data will include determination of complete (CR) and partial response (PR) rates, as well as stable (SD) and progressive disease (PD).
21 days after cycle 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2005

Primary Completion (ACTUAL)

April 1, 2010

Study Registration Dates

First Submitted

January 19, 2007

First Submitted That Met QC Criteria

January 19, 2007

First Posted (ESTIMATE)

January 23, 2007

Study Record Updates

Last Update Posted (ACTUAL)

December 5, 2018

Last Update Submitted That Met QC Criteria

November 9, 2018

Last Verified

November 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6308 (FH/UWCC ID)
  • 127 (Tumor Vaccine Group)
  • NCI-2010-00800 (REGISTRY: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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