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

Primary Purpose

Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ONTAK
flow cytometry
immunohistochemistry staining method
enzyme-linked immunosorbent assay
laboratory biomarker analysis
protein expression analysis
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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 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.

Outcomes

Primary Outcome Measures

Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
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.
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
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.

Secondary Outcome Measures

Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
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.
Presence of Circulating sIL-2R in the Peripheral Blood
Evaluate levels of circulating sIL-2R (pg/ml) in the peripheral blood assessed before and after ONTAK therapy. Changes from baseline will be tabulated.
Presence of Endogenous Tumor-specific Immunity
Evaluate the effect of ONTAK on endogenous tumor specific immunity
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
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).

Full Information

First Posted
January 19, 2007
Last Updated
November 9, 2018
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00425672
Brief Title
ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment
Official Title
Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
September 2005 (Actual)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Breast Cancer, Recurrent Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
ONTAK
Other Intervention Name(s)
DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DAB389IL-2, denileukin diftitox, DAB389IL2, DABIL2
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Other Intervention Name(s)
immunohistochemistry
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)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
protein expression analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Safety Evaluated by Collecting Study Related Toxicity as Assessed by CTCAE v3.0
Description
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.
Time Frame
7 Days after last dose of ONTAK
Title
Efficacy of ONTAK in Depleting T-regulatory Cells as a Decrease in Peripheral Blood Tregs Using Flow Cytometry
Description
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.
Time Frame
21 days after cycle 6
Secondary Outcome Measure Information:
Title
Incidence of Interleukin-2 (IL-2) and IL-2 Receptor (IL-2R) Expression in Tumor Samples by Immunohistochemical (IHC) Analysis
Description
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.
Time Frame
21 days after cycle 6
Title
Presence of Circulating sIL-2R in the Peripheral Blood
Description
Evaluate levels of circulating sIL-2R (pg/ml) in the peripheral blood assessed before and after ONTAK therapy. Changes from baseline will be tabulated.
Time Frame
21 days after cycle 6
Title
Presence of Endogenous Tumor-specific Immunity
Description
Evaluate the effect of ONTAK on endogenous tumor specific immunity
Time Frame
21 days after cycle 6
Title
Anti-tumor Effects of ONTAK Determined by Tumor Response and Progression
Description
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).
Time Frame
21 days after cycle 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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

12. IPD Sharing Statement

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

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