Clinical trial NCT00847171
Conditions: Breast Cancer
Keywords: male breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer HER2-positive breast cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2008-12-01; Completion date: 2013-06-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: 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. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. Giving trastuzumab together with cyclophosphamide and vaccine therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving trastuzumab together with cyclophosphamide and vaccine therapy in treating patients with high-risk or metastatic breast cancer.

Detailed description:
OBJECTIVES:

Primary

* To evaluate the safety of allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine in combination with trastuzumab (Herceptin®) and cyclophosphamide in patients with high-risk or metastatic HER2/neu-overexpressing breast cancer.
* To measure the HER2/neu-specific CD4+ T-cell response by delayed-type hypersensitivity.
* To measure the magnitude of HER2/neu-specific CD8+ T-cell responses by ELISPOT.

Secondary

* To assess the impact of trastuzumab on immune priming in vivo by IHC.
* To measure the impact of cyclophosphamide pretreatment on CD4+CD25+ regulatory T cells by flow cytometry.
* To determine the time to disease progression.

Tertiary

* To develop the tandem tetramer/CD107a cytotoxicity assay for HER2/neu-specific CD8+ T cells.
* To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.

OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day -1 of the first course of vaccination and continuing until the completion of the last course of vaccination. Patients also receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine intradermally on day 0. Treatment with cyclophosphamide and the vaccine repeats every 27-42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth course of cyclophosphamide and vaccine approximately 6-8 months after the first course.

Patients undergo delayed-type hypersensitivity testing and blood sample collection at baseline and periodically during study for immunologic laboratory studies. Blood samples are analyzed for serum GM-CSF levels by pharmacokinetic studies and for immune monitoring by ELISPOT and flow cytometry. Skin punch biopsies are also performed periodically and analyzed by IHC.

After completion of study treatment, patients are followed periodically.

Arms: arm 1: Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Interventions: intervention 1: allogeneic GM-CSF-secreting breast cancer vaccine intervention 2: trastuzumab intervention 3: cyclophosphamide intervention 4: flow cytometry intervention 5: immunoenzyme technique intervention 6: immunohistochemistry staining method intervention 7: laboratory biomarker analysis intervention 8: pharmacological study intervention 9: biopsy
Intervention descriptions: intervention 1: Day 0 : Allogeneic GM-CSF-secreting Breast Cancer Vaccine administered as:

12 intradermal injections of a divided total dose of 5 x108 cells. intervention 2: Patient HAS received prior Trastuzumab within the last two weeks, give Trastuzumab 2 mg/kg weekly on Day -1 for 5 weeks.

Patient has NOT received Trastuzumab within the last two weeks, give On Cycle 1, Day -1 ONLY, Loading dose 4 mg/kg intervention 3: Cyclophosphamide 200mg/m2 IV in NS 100ml over 30 minutes on Day -1 ONLY. Note: there are no dose modifications for Cyclophosphamide. intervention 4: Samples will be analyzed by flow cytometry using Cell Quest software intervention 5: None intervention 6: Measuring Immune Priming In Vivo By Vaccine Site Biopsies intervention 7: None intervention 8: None intervention 9: skin biopsy to be performed on day 3 and day 7 for cycle 1 and 3 only

Protocol documents: