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
N/A
N/A
Both
HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
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
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.
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
Type of Study:
Interventional
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:
No
Principal Investigator
Charles Shapiro
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01402
NCT ID:
NCT00006228
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
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
