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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

Phase 2
Not Enrolling
HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

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Trial Information

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


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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Time Frame:

Up to 12 months

Safety Issue:


Principal Investigator

Charles Shapiro

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

July 2000

Completion Date:

Related Keywords:

  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male



Ohio State University Medical Center Columbus, Ohio  43210