Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patients With High-Risk or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00847171|
Recruitment Status : Completed
First Posted : February 19, 2009
Results First Posted : September 26, 2018
Last Update Posted : September 26, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||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||Phase 2|
- 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.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Safety and Bioactivity Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-Secreting Breast Tumor Vaccine for the Treatment of Patients With High Risk/ Metastatic HER-2/Neu- Overexpressing Breast Cancer With No Evidence of Disease|
|Study Start Date :||December 2008|
|Actual Primary Completion Date :||June 2013|
|Actual Study Completion Date :||June 2013|
Experimental: Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine
Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Day 0 : Allogeneic GM-CSF-secreting Breast Cancer Vaccine administered as:
12 intradermal injections of a divided total dose of 5 x108 cells.
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
Other Name: Herceptin
Cyclophosphamide 200mg/m2 IV in NS 100ml over 30 minutes on Day -1 ONLY. Note: there are no dose modifications for Cyclophosphamide.
Other Name: Cytoxan
Other: flow cytometry
Samples will be analyzed by flow cytometry using Cell Quest software
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Measuring Immune Priming In Vivo By Vaccine Site Biopsies
Other: laboratory biomarker analysis
Other: pharmacological study
skin biopsy to be performed on day 3 and day 7 for cycle 1 and 3 only
- Safety as Assessed by Number of Participants Experiencing Toxicity [ Time Frame: 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.
- Number of Participants With Immunologic Response as Determined by Delayed-type Hypersensitivity (DTH) Response to HER2/Neu-derived Peptides [ Time Frame: 4 years ]
- Clinical Benefit as Assessed by Number of Participants With Progression-free Survival [ Time Frame: 4 years ]Number of participants without evidence of disease progression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00847171
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Principal Investigator:||Leisha A. Emens, MD, PhD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|