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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00425672
First received: January 19, 2007
Last updated: May 7, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
 Biological: ONTAK
Other: flow cytometry
Other: immunohistochemistry staining method
Other: enzyme-linked immunosorbent assay
Other: laboratory biomarker analysis
Genetic: protein expression analysis
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I-II Study of Denileukin Diftitox (ONTAK®) in Patients With Advanced Refractory Breast Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Safety and systemic toxicity as assessed by CTCAE v3.0 [ Time Frame: 7 Days after last dose of ONTAK ] [ Designated as safety issue: Yes ]
    Initial evaluation, 3 weeks after cycles 2, 4, and 6

  • Efficacy of ONTAK in depleting T-regulatory cells [ Time Frame: 21 days after cycle 6 ] [ Designated as safety issue: No ]
    Initial evaluation, 3 weeks after cycles 2, 4, and 6


Secondary Outcome Measures:
  • Incidence of interleukin-2 (IL-2) and IL-2 receptor (IL-2R) expression in tumor samples [ Time Frame: 21 days after cycle 6 ] [ Designated as safety issue: No ]
    Initial evaluation, 3 weeks after cycles 2, 4, and 6

  • Presence of circulating sIL-2R in the peripheral blood [ Time Frame: 21 days after cycle 6 ] [ Designated as safety issue: No ]
    Initial Evaluation, 3 weeks after cycle 2, 4, 6

  • Presence of endogenous tumor-specific immunity [ Time Frame: 21 days after cycle 6 ] [ Designated as safety issue: No ]
    Initial Evaluation, 3 weeks after cycle 2, 4, 6

  • Anti-tumor effects of ONTAK determined by tumor response and progression [ Time Frame: 21 days after cycle 6 ] [ Designated as safety issue: No ]
    Initial Evaluation, 3 weeks after cycle 2, 4, 6


Estimated Enrollment: 15
Study Start Date: September 2005
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 Biological: ONTAK
Given IV
Other Names:
  • DAB389 interleukin-2
  • DAB389 interleukin-2 immunotoxin
  • DAB389-IL2
  • DAB389IL-2
  • denileukin diftitox
  • DAB389IL2
  • DABIL2
Other: flow cytometry
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: laboratory biomarker analysis
Correlative studies
Genetic: protein expression analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00425672

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lupe Salazar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00425672     History of Changes
Obsolete Identifiers: NCT00364208
Other Study ID Numbers: 6308, NCI-2010-00800, 127
Study First Received: January 19, 2007
Last Updated: May 7, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Denileukin diftitox
Interleukin-2
Antineoplastic Agents
 Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 16, 2013