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Trastuzumab and Interleukin-2 in Treating Patients With Metastatic Breast Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00006228
First Posted: January 27, 2003
Last Update Posted: October 8, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Interleukin-2 may stimulate a person's white blood cells to kill breast cancer cells. Phase II trial to study the effectiveness of trastuzumab plus interleukin-2 in treating patients who have metastatic breast cancer that has not responded to previous trastuzumab therapy.

Condition Intervention Phase
HER2-positive Breast Cancer Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Biological: trastuzumab Biological: aldesleukin Other: laboratory biomarker analysis Other: pharmacological study Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Anti-HER-2 Monoclonal Antibody Trastuzumab (Herceptin) in Combination With Low Dose Interleukin-2 (Proleukin) in Metastatic Breast Cancer Patients Who Have Previously Failed Trastuzumab

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 12 months ]
  • Toxicity assessed using Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: Up to 12 months ]

Secondary Outcome Measures:
  • Degree of NK cell expansion [ Time Frame: Up to 12 months ]
  • Effectiveness of patients' PBMCs in a standard ADCC assay directed against HER2 target cells [ Time Frame: Up to 12 months ]

Estimated Enrollment: 37
Study Start Date: July 2000
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (trastuzumab and aldesleukin)
Patients receive trastuzumab IV over 30-90 minutes on days 1 and 8 and aldesleukin SC on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.
Biological: trastuzumab
Given IV
Biological: aldesleukin
Given SC
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the response rate and toxicity to low-dose IL-2 with intermediate-"pulse" dose interleukin 2 (IL-2) and trastuzumab in patients with uni-dimensional measurable metastatic breast cancer and human epidermal growth factor receptor 2 (HER2) positive (3+ overexpression by immunohistochemistry [IHC] method or positive by fluorescent in situ hybridization [FISH]) who either have had evidence of progressive disease while receiving a trastuzumab-containing regimen, or have had progressive disease within 12 months of receiving a trastuzumab-containing regimen.

SECONDARY OBJECTIVES:

I. To perform correlative immunologic assays to determine the degree of natural killer (NK) cell expansion in response to low-dose IL-2, and the effectiveness of patients' peripheral blood mononuclear cells (PBMC) in a standard antibody-dependent cell-mediated cytotoxicity (ADCC) assay directed against a HER2 target cell.

II. To determine the pharmacokinetics of trastuzumab using an every 2-week schedule.

III. To determine Fc-gamma receptor polymorphisms from study patients.

OUTLINE: This is a multicenter study.

Patients receive trastuzumab intravenously (IV) over 30-90 minutes on days 1 and 8 and aldesleukin subcutaneously (SC) on days 2-7 and 9-21. Beginning on day 22, patients receive trastuzumab IV over 30 minutes every 14 days. Patients also receive aldesleukin SC daily on days 1-14. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days.

PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed breast cancer

    • Primary and/or metastatic disease
  • HER2 overexpression 3+ by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)

    • Tumors with HER2 2+ overexpression by IHC allowed if confirmed by FISH
  • Progressive disease during or within 12 months of receiving prior regimen containing trastuzumab (Herceptin)
  • Unidimensionally measurable disease

    • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
    • The following are not considered measurable:

      • Bone metastases
      • Pleural or peritoneal effusion
      • Ascites
      • Leptomeningeal disease
      • Lymphangitic disease
      • Inflammatory breast cancer
      • Cystic lesions
      • CNS lesions
  • CNS metastases allowed if all of the following conditions are met:

    • Asymptomatic
    • At least 3 months since prior surgery and/or cranial irradiation
    • At least 3 weeks since prior steroids
  • Hormone receptor status:

    • Not specified
  • Male or female
  • Performance status - ECOG 0-2
  • Granulocyte count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT and SGPT no greater than 2 times ULN (5 times ULN for liver metastases)
  • Alkaline phosphatase no greater than 2 times ULN (5 times ULN for liver metastases)
  • Creatinine no greater than 1.5 times ULN
  • LVEF at least lower limit of normal by MUGA or echocardiogram
  • No congestive heart failure or active ischemic heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No psychiatric illness, medical condition, or uncontrolled infection that would preclude study
  • No underlying immunodeficiency (e.g., HIV or autoimmune disease)
  • No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • See Disease Characteristics
  • Prior cumulative doxorubicin dose no greater than 360 mg/m^2
  • At least 3 weeks since prior chemotherapy
  • No more than 2 prior chemotherapy regimens for metastatic disease
  • No concurrent chemotherapy
  • See Disease Characteristics
  • At least 3 weeks since prior endocrine therapy
  • No concurrent corticosteroids or dexamethasone
  • Concurrent hormones allowed for conditions unrelated to disease (e.g., insulin for diabetes)
  • See Disease Characteristics
  • At least 3 weeks since prior radiotherapy
  • No prior radiotherapy to study lesion, unless evidence of disease progression
  • No concurrent palliative radiotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior major surgery
  • No concurrent immunosuppressive drugs
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006228


Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Charles Shapiro Ohio State University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006228     History of Changes
Other Study ID Numbers: NCI-2012-01402
NCI-2012-01402 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000068150
OSU-99H0192
OSU-9945
NCI-195
9945 ( Other Identifier: Ohio State University Medical Center )
195 ( Other Identifier: CTEP )
N01CM17102 ( U.S. NIH Grant/Contract )
First Submitted: September 11, 2000
First Posted: January 27, 2003
Last Update Posted: October 8, 2013
Last Verified: October 2013

Additional relevant MeSH terms:
Breast Neoplasms, Male
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aldesleukin
Trastuzumab
Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents