Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patients With High-Risk or Metastatic Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer

Interventions: Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Biological: trastuzumab
Drug: cyclophosphamide
Other: flow cytometry
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: biopsy

Registration Number: NCT00847171

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	trastuzumab	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	laboratory biomarker analysis	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	allogeneic GM-CSF-secreting breast cancer vaccine	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	cyclophosphamide	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	flow cytometry	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	immunohistochemistry staining method	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	biopsy	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	immunoenzyme technique	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine	pharmacological study	Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine

Primary Outcome Measures

Name	Time	Method
Number of Participants With Immunologic Response as Determined by Delayed-type Hypersensitivity (DTH) Response to HER2/Neu-derived Peptides	4 years
Safety as Assessed by Number of Participants Experiencing Toxicity	4 years	Safety as assessed by number of participants who experienced drug-related local and systemic toxicity, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0) in response to CY-modulated immunization with a novel breast cancer vaccine in the setting of weekly Trastuzumab therapy.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit as Assessed by Number of Participants With Progression-free Survival	4 years	Number of participants without evidence of disease progression.