Trastuzumab and Interleukin-2 in Treating Patients With Metastatic Breast Cancer
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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: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | PHASE II TRIAL OF ANTI-HER2 MONOCLONAL ANTIBODY TRASTUZUMAB (HERCEPTINî) IN COMBINATION WITH LOW DOSE INTERLEUKIN-2 (PROLEUKINî) IN METASTATIC BREAST CANCER PATIENTS WHO HAVE PREVIOUSLY FAILED TRASTUZUMAB |
- 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 ]
- 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 ]
| Enrollment: | 37 |
| Study Start Date: | January 2001 |
| Primary Completion Date: | July 2009 (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
Other Names:
Biological: aldesleukin
Given SC
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological 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| 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| United States, Ohio | |
| Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | |
| Columbus, Ohio, United States, 43210 | |
| Principal Investigator: | Charles Shapiro | Ohio State University Comprehensive Cancer Center |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00006228 History of Changes |
| Other Study ID Numbers: | NCI-2012-01402, 9945, N01CM17102, CDR0000068150 |
| Study First Received: | September 11, 2000 |
| Last Updated: | December 5, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Breast Neoplasms Breast Neoplasms, Male Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Aldesleukin Trastuzumab Interleukin-2 Antineoplastic Agents Therapeutic Uses |
Pharmacologic Actions Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on May 23, 2013