Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00971737|
Recruitment Status : Completed
First Posted : September 4, 2009
Results First Posted : March 12, 2019
Last Update Posted : April 24, 2019
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and trastuzumab, may increase the number of immune cells and make the immune response stronger. It is not yet known whether giving cyclophosphamide together with vaccine therapy is more effective with or without trastuzumab in treating patients with metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying the side effects of giving cyclophosphamide together with vaccine therapy and to see how well it works compared with giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients with metastatic breast cancer.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Biological: allogeneic GM-CSF-secreting breast cancer vaccine Biological: trastuzumab Drug: cyclophosphamide||Phase 2|
- To evaluate the safety of cyclophosphamide-modulated vaccination with vs without trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.
- To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs without trastuzumab in these patients.
- To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type hypersensitivity (DTH) and ELISPOT.
- To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.
- To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry of vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms, comparing cellular infiltrates to those seen in previous preclinical and clinical models.
- To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.
- To characterize the peripheral-memory T-cell pool.
- To determine baseline and change in vaccine site-draining lymph node immunohistology and gene expression profile.
- To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T cells.
- To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
- Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of courses 1 and 3 for biomarker analysis.
After completion of study treatment, patients are followed periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||63 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||July 2009|
|Actual Primary Completion Date :||March 2016|
|Actual Study Completion Date :||March 2016|
Active Comparator: Cyclophosphamide and Vaccine only
Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Experimental: Cyclophosphamide, Vaccine and Trastuzumab
Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
Biological: allogeneic GM-CSF-secreting breast cancer vaccine
- Toxicity as Assessed by Number of Grade 3 or 4 Adverse Events [ Time Frame: 3 years ]Number of grade 3 or 4 nonhematologic toxicity (except alopecia), or any grade 4 hematologic toxicity as defined by NCI CTCAE v3.0
- Clinical Benefit (CB) as Assessed by Progression Free Survival at Six Months [ Time Frame: 6 months post-intervention ]Progression-free survival is measured as percentage of participants with stable disease or complete response, as defined by RECIST criteria, six months after receiving last vaccination. Progressive disease (PD) will be defined by the appearance of a new lesion, or by an increase of at least 20% in the sum of the longest diameter of target lesions, taking as a reference that smallest sum longest diameter recorded since the study intervention began. In the case of bone lesions, progressive disease will be established after eight weeks of increasing or new lesions if there is subjective progressive disease as noted by increasing bone pain or decreasing performance status. These observations must be present for at least two measurement periods separated by at least four weeks.
- HER-2/Neu-specific Immune Responses as Measured by Number of Participants With Positive for Delayed-type Hypersensitivity (DTH) Response [ Time Frame: 3 years ]
- Pharmacodynamics of Peripheral CD4+CD25+ Regulatory T Cells [ Time Frame: 3 years ]
- Immune Priming in In-vivo Vaccine-site Biopsies [ Time Frame: 3 years ]
- Enumeration of CD8+ T Cells Specific for hTERT by ELISPOT [ Time Frame: 3 years ]
- Characterization of the T-cell Memory Pool Pre- and Post-vaccination [ Time Frame: 3 years ]
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): NCT00971737
|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|