Clinical trial NCT00824733
Conditions: Breast Cancer
Keywords: recurrent breast cancer stage IV breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer HER2-positive breast cancer male breast cancer
Sponsor: Bhuvaneswari Ramaswamy
Start date: 2009-02-01; Completion date: 2014-04-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving agatolimod together with trastuzumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving agatolimod together with trastuzumab works in treating patients with locally advanced or metastatic breast cancer.

Detailed description:
OBJECTIVES:

Primary

* To evaluate the progression-free survival of patients with HER2-overexpressing locally advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and agatolimod sodium.

Secondary

* To determine if agatolimod sodium augments antibody-mediated cytoxicity (ADCC) against trastuzumab-coated target cells by evaluating the ability of patient immune-effector cells to conduct ADCC and produce interferon gamma.

OUTLINE: This is a multicenter study.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients also receive agatolimod sodium subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for correlative laboratory studies. Samples are analyzed for antibody-mediated cytotoxicity (ADCC) by chromium-release assay; IFN-γ production and quantification by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR); and levels of cytokines (IFN-γ and TNF-α) by ELISA.

After completion of study therapy, patients are followed periodically.

Arms: arm 1: 12 weekly treatments. Week 1-12 patients will receive Trastuzumab 2mg/kg IV(intervenous infusion). Patients who have not been treated wih Trastuzumab within 4 weeks will receive a loading dose of 4 mg/kg on week 1 and PF-03512676-0.16 mg/kg subcutaneous injection.Correlative studies will be drawn on week 1, 2, 6, 12 and 18.
Interventions: intervention 1: Trastuzumab intervention 2: PF03512676 intervention 3: Correlative Studies
Intervention descriptions: intervention 1: IV at 2 mg/kg over 30 minutes on day 1 of each weekly cycle. Patients who have not received trastuzumab for 4 weeks or more will receive a loading dose of 4 mg/kg over 90 minutes day 1 of the first cycle. The dose of trastuzumab will be based on the patient's actual weight at the start of each 4 week treatment cycle. intervention 2: Patients also receive PF03512676 subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. intervention 3: Blood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18.

Protocol documents: