J0947, A Randomized, Open-Label Comparative Study of Combination Therapy with Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer that Does NOT Over-express HER-2/neu
This is a comparison trial designed to evaluate whether adding Trastuzumab (T) to low doses of Cyclophosphamide (CY) sequenced with an allogeneic GM-CSF-secreting whole cell breast cancer vaccine can enhance vaccine-activated immunity in patients with Stage IV breast cancer that does not overexpress HER-2/neu. Both Trastuzumab and CY are known to have immunomodulatory effects that might enhance vaccine activity. The purpose of this study is to determine the safety of the two combination vaccine therapies, and to evaluate whether Trastuzumab combined with CY can make the vaccine work better than CY alone.
This study is open to adult men and women with metastatic breast cancer that does not over-express HER-2/neu. Patients currently on hormonal and/or bisphosphonate therapy are eligible for this study.
Patients will sign the informed consent to participate, they will be evaluated for eligibility to participate. This will consist of a clinical examination, radiological evaluation of disease status and cardiac function as well as tumor markers and blood profiles. Eligible patients will be divided into two groups as shown in Figure A; they will not be able to choose which group they are in. In one group patients will receive repeated cycles of CY and vaccine every four to six weeks for up to four complete cycles. In the second group patients will received repeated cycles of CY, Trastuzumab and vaccine every four to six weeks for up to four complete cycles. Patients will be evaluated clinically and with laboratory testing for evidence of disease progression after each cycle or when otherwise clinically indicated. Computed tomography (CT scan) of the chest, abdomen, and pelvis and nuclear medicine bone scan will also be performed to evaluate disease status prior to starting the study, after vaccine cycle 3, and prior to and after vaccine cycle 4. During each cycle as shown in Figure B, patients will receive 200 mg/m2 CY or CY plus Trastuzumab on day â??1, and the vaccine containing a mixture of two GM-CSF-secreting allogeneic breast cancer cell lines (two parts 2T47D-V and one part 3SKBR3-7 mixed in a fixed dose of 5 X 108 cells for each patient and each vaccination cycle) on day 0. In addition to the laboratory studies shown, hematologic profiles and blood chemistries will be assessed to screen for acute toxicities. Skin punch biopsies (3mm) will be obtained at baseline and on days +3 and +7 of vaccine cycles 1 and 3 only. Lymph node biopsies will also be obtained at baseline and on days +3 and +7 of vaccine cycles 1 and 3 only. OPTIONAL leukopheresis will be obtained after vaccine cycle # 3 only.
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