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

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

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.

Study Overview

• Status: Completed
• Conditions: HER2-positive Breast Cancer; Male Breast Cancer; Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Biological: trastuzumab; Biological: aldesleukin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Biological: trastuzumab; Given IV; Biological: aldesleukin; Given SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate using Response Evaluation Criteria in Solid Tumors (RECIST)	Up to 12 months
Toxicity assessed using Common Toxicity Criteria (CTC) version 2.0	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Degree of NK cell expansion	Up to 12 months
Effectiveness of patients' PBMCs in a standard ADCC assay directed against HER2 target cells	Up to 12 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): July 1, 2003

Study Registration Dates

• First Submitted: September 11, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): October 8, 2013
• Last Update Submitted That Met QC Criteria: October 7, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Aldesleukin; Trastuzumab
• Other Study ID Numbers: NCI-2012-01402 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); N01CM17102 (U.S. NIH Grant/Contract); 9945 (Ohio State University Medical Center); CDR0000068150; OSU-99H0192; OSU-9945; NCI-195; 195 (CTEP)