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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Male Breast Cancer; HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Treatments: Biological: trastuzumab; Biological: aldesleukin; Other: pharmacological study; Other: laboratory biomarker analysis

Study type: Interventional

Funder types: NIH

Identifiers

NCT00006228

OSU-9945

CDR0000068150

195 (Other Identifier)

N01CM17102 (U.S. NIH Grant/Contract)

NCI-2012-01402 (Registry Identifier)

9945 (Other Identifier)

NCI-195

OSU-99H0192

Details and patient eligibility

About

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.

Full 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.

Enrollment: 37 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

37 participants in 1 patient group

Treatment (trastuzumab and aldesleukin)

Experimental group

Description:

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.

Treatment:

Biological: aldesleukin

Biological: trastuzumab

Other: pharmacological study

Other: laboratory biomarker analysis