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

HER2-positive Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006228
• Other study ID #: NCI-2012-01402
• Secondary ID: NCI-2012-01402CD
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2000
• Last updated: October 7, 2013
• Start date: July 2000

Study information

• Verified date: October 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Biological:
• trastuzumab
Given IV
• aldesleukin
Given SC

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)		Up to 12 months	No
Primary	Toxicity assessed using Common Toxicity Criteria (CTC) version 2.0		Up to 12 months	Yes
Secondary	Degree of NK cell expansion		Up to 12 months	No
Secondary	Effectiveness of patients' PBMCs in a standard ADCC assay directed against HER2 target cells		Up to 12 months	No