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

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00425672

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 I Phase II

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Male Breast Cancer

Drug Information available for: Interleukin-2 Denileukin diftitox

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

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

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

Fred Hutchinson Cancer Research Center

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:	Salazar, Lupe, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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:	June 7, 2011
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 February 09, 2012