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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: September 11, 2000
Last updated: October 7, 2013
Last verified: October 2013

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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]
  • Toxicity assessed using Common Toxicity Criteria (CTC) version 2.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Degree of NK cell expansion [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Effectiveness of patients' PBMCs in a standard ADCC assay directed against HER2 target cells [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

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:


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.


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.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
Please refer to this study by its identifier: NCT00006228

United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Principal Investigator: Charles Shapiro Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00006228     History of Changes
Other Study ID Numbers: NCI-2012-01402, NCI-2012-01402, CDR0000068150, OSU-99H0192, OSU-9945, NCI-195, 9945, 195, N01CM17102
Study First Received: September 11, 2000
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Breast Diseases
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents processed this record on April 15, 2014