Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00399529|
Recruitment Status : Completed
First Posted : November 15, 2006
Results First Posted : April 13, 2020
Last Update Posted : April 22, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Neoplasms||Biological: Allogeneic GM-CSF-secreting breast cancer vaccine Drug: Trastuzumab Drug: Cyclophosphamide||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Feasibility Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for HER-2/Neu-Overexpressing Metastatic Breast Cancer.|
|Study Start Date :||September 2006|
|Actual Primary Completion Date :||February 2010|
|Actual Study Completion Date :||February 2010|
Experimental: Allo GM-CSF-secreting vaccine, Trastuzumab, Cyclophosphamide
Allogeneic GM-CSF-secreting breast cancer vaccine : 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 10^8 cells for each patient and each vaccination cycle) given intradermally every 4-6 weeks for 3 cycles and then a 4th dose given 6-8 months after beginning the study.
Trastuzumab : An initial loading dose of 4 mg/kg for participants beginning treatment with Trastuzumab, otherwise 2 mg/kg given every week intravenously
Cyclophosphamide : 300 mg/m^2 given intravenously every 4-6 weeks for 3 cycles and then once 6-8 months after beginning the study
Biological: Allogeneic GM-CSF-secreting breast cancer vaccine
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.
Trastuzumab is a humanized monoclonal antibody specific for the extracellular domain of HER-2/neu that is now one component of the standard of care for both early and late stage HER-2/neu-overexpressing breast cancers. It exerts a pleiotropic antitumor effect by multiple mechanisms. The antibody decreases heterodimer formation with other members of the epidermal growth factor receptor (EGFR) family, thereby indirectly inhibiting signaling through the Ras/Raf/mitogen-activated protein kinases (MAPK) and Phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) pathways. It also inhibits tumor neovascularization, and augments apoptosis both in vitro and in vivo. Trastuzumab prevents cleavage of the extracellular domain of HER-2/neu, thus abrogating the constitutive activation of the remaining membrane-associated intracellular domain.
Other Name: Herceptin
The doses of Cyclophosphamide are based on previously reported clinical experience as well as our own preclinical data demonstrating augmented vaccine efficacy with CY-modulated vaccination. In particular, 300 mg/m2
Other Name: Cytoxan
- Number of Participants With Adverse Events [ Time Frame: From first dose through 30 days after last dose of study drug, up to 9 months ]Safety is measured as the number of patients that experienced adverse events related to study drug.
- Number of Participants With Clinical Benefit [ Time Frame: At 6 and 12 months from start of treatment ]Clinical benefit is defined as the proportion of patients achieving complete response, partial response, or stable disease by RECIST. Complete response (CR) is defined as total disappearance of all clinical evidence of reversible disease. A partial response (PR) is defined as a >=30% reduction in tumor target lesions. Stable disease (SD) is defined as disease status that fails to qualify as as a response (CR or PR) or progressive disease (increase of at least 20% in tumor target lesions).
- Number of Participants With Delayed Type Hypersensitivity (Immunological Response) [ Time Frame: 30 days after each vaccine, up to 9 months ]The number of participants with a Delayed Type Hypersensitivity (DTH) response was measured as an indicator of immune response. Participants were considered to have a DTH response if they had increased induration (>5mm from baseline) at the site of injection 2-3 days after intradermal injection with human epidermal growth factor receptor 2 (HER-2) peptides. This peptide injection was given 28 days after each dose of vaccine.
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): NCT00399529
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Leisha A Emens, M.D.,Ph.D.||Johns Hopkins University|