Clinical trial NCT00006228: Trastuzumab and Interleukin-2 in Treating Patients With Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2-positive Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 37
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Up to 12 months
measure: Toxicity assessed using Common Toxicity Criteria (CTC) version 2.0
timeFrame: Up to 12 months
Secondary outcomes:
measure: Degree of NK cell expansion
timeFrame: Up to 12 months
measure: Effectiveness of patients' PBMCs in a standard ADCC assay directed against HER2 target cells
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Charles Shapiro
role: PRINCIPAL_INVESTIGATOR
References: