Denileukin Diftitox 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:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00425672

Purpose

RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to breast cancer cells.

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

Condition	Intervention	Phase
Breast Cancer	Biological: denileukin diftitox Genetic: protein expression analysis Other: flow cytometry Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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

Drug Information available for: Denileukin diftitox

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety and systemic toxicity as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
Efficacy of denileukin diftitox in depleting T-regulatory cells (Tregs) as measured by flow cytometry [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of interleukin-2 (IL-2) and IL-2 receptor (IL-2R) expression in tumor samples as measured by immunochemistry [ Designated as safety issue: No ]
Presence of circulating IL-2R in the peripheral blood as measured by ELISA [ Designated as safety issue: No ]
Presence of endogenous tumor-specific immunity as measured by ELIspot [ Designated as safety issue: No ]
Tumor response and progression as measured by RECIST criteria [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	September 2005
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety of denileukin diftitox in patients with refractory advanced breast cancer.
Assess the effect of this drug on peripheral blood T-regulatory suppressor cells (Tregs).

Secondary

Determine the incidence of interleukin-2 receptor (IL-2R) expression in tumor samples from these patients.
Correlate tumor IL-2R expression with tumor response to denileukin diftitox.
Assess levels of circulating IL-2R before and after treatment with this drug.
Determine the effect of this drug on endogenous tumor-specific immunity.
Determine the potential antitumor effects of this drug in these patients.

OUTLINE: This is a nonrandomized study.

Patients receive denileukin diftitox 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.

Blood samples are collected at baseline and periodically during study treatment. Some patients may undergo additional blood sample collection at 3 and 6 months after study treatment. T-regulatory cells (Tregs) are quantified using flow cytometry. The presence of endogenous tumor-specific immunity is evaluated using immunoenzyme techniques to detect tumor markers, including HER-2/neu, carcinoembryonic antigen (CEA), MAGE-3, and circulating interleukin-2 receptor (IL-2R). Tumor samples are collected at baseline and evaluated by immunohistochemistry for IL-2 and IL-2R (α, β, γ) expression.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of refractory advanced breast cancer
- Progressive or relapsed disease after standard therapy
Measurable disease that may include, but is not limited to, the bone
- Measurable extraskeletal disease that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional CT scan OR ≥ 10 mm by spiral CT scan
- Bidimensionally measurable chest wall disease allowed
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Male or female
Menopausal status not specified
ECOG performance status 0-2
WBC > 3,000/mm³
Absolute neutrophil count > 1,000/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min
ALT and AST ≤ 2.0 times upper limit of normal (ULN)
Total bilirubin ≤ 1.5 times ULN
Albumin ≥ 3.0 g/dL
Recovered from major infections
Not pregnant or nursing
Fertile patients must use effective contraception during and for 1 month after completion of study treatment
No active autoimmune disease
No known pulmonary disease except controlled asthma
No known hypersensitivity to diphtheria toxin or aldesleukin
No New York Heart Association class III-IV heart disease
No significant, active concurrent medical illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior surgical procedures
At least 14 days since prior cytotoxic chemotherapy
No prior treatment with denileukin diftitox or DAB (486) interleukin-2
Concurrent bisphosphonates allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00425672

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Nicole Bates 206-543-6620
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Lupe G. Salazar, MD

Seattle Cancer Care Alliance

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Washington School of Medicine ( Lupe G. Salazar )
Study ID Numbers:	CDR0000526414, UWCC-6308, UWCC-05-6951-A
Study First Received:	January 19, 2007
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00425672 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IIIB breast cancer
male breast cancer
recurrent breast cancer
stage IV breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:

Skin Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Breast Neoplasms
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Interleukin-2

Analgesics, Non-Narcotic
Sensory System Agents
Denileukin diftitox
Therapeutic Uses
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Breast Diseases

ClinicalTrials.gov processed this record on November 27, 2009