A Safety and Immunology Study of a Modified Vaccinia Vaccine for HER-2(+) Metastatic Breast Cancer
The current trial, BNIT-BR-002, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2, with and without Herceptin, following 1st- or 2nd-line chemotherapy in patients with Her-2-positive metastatic breast cancer.
The intent of vaccination is to induce anti-Her-2 immune responses, both antibody and T cell, that will then attack the Her-2 expressing tumors, and may induce tumor regression or slow progression of disease.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of a Fixed Dose of MVA-BN-HER2 Following 1st- or 2nd-Line Chemotherapy for HER-2-Positive Metastatic Breast Cancer|
- Safety and tolerability [ Time Frame: 2years, 3 months ] [ Designated as safety issue: No ]
- Immune response [ Time Frame: 2 yrs 3 mo ] [ Designated as safety issue: No ]
|Study Start Date:||June 2007|
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
MVA-BN®-HER2 is a candidate breast cancer immunotherapy product comprised of a highly attenuated non-replicating vaccinia virus, MVA-BN®, engineered to encode a modified form of the Her-2 protein.
MVA-BN® is a well-characterized, clonal strain of modified vaccinia virus Ankara (MVA) being developed as a smallpox vaccine, suitable for use in high-risk (e.g., immunocompromised) individuals. MVA-BN®-derived vectors encoding heterologous antigens are being developed for use as vaccines for infectious diseases such as HIV, and for the treatment of cancer. A large database exists from safety evaluations in animals and in humans for MVA-BN®, and MVA-BN®-derived vectors.
Her-2 is overexpressed in 20-30% of human breast cancers. It is an oncogene/growth factor receptor critical for malignant phenotype of Her-2 expressing tumors. It is an immunogenic target, and immune responses to this protein have been shown to mediate potent anti-tumor activity in multiple animal models. Means to stimulate anti-Her-2 reactivity are now being studied clinically. Sponsor, collaborators, and others have used both Protein and DNA vaccine forms of Her-2, and a safety database is developed and no significant adverse events have resulted from Her-2 directed vaccination.
MVA-BN®-HER2 encodes a modified form of the Her-2 protein, hereinafter referred to as HER2. HER2 contains the extracellular domain of Her-2 but lacks the intracellular, cell signaling domain. In addition, HER2 includes two universal T-cell epitopes from tetanus toxin to facilitate the stimulation of an immune response to Her-2, a self-protein.
The current trial, BNIT-BR-002, will evaluate the safety and biological activity of a fixed dose of MVA-BN®-HER2, with and without Herceptin, following 1st- or 2nd-line chemotherapy in patients with metastatic breast cancers which overexpress Her-2.
Patients will receive 3 subcutaneous vaccinations at 3 week intervals and have tumor followed by CT/MRI imaging and blood drawn for immune function analysis.
|United States, California|
|Alta Bates Herrick Hospital Comprehensive Cancer Center|
|Berkeley, California, United States, 94705|
|Stanford Cancer Center|
|Stanford, California, United States, 94305|
|Study Director:||Olga Bandman||Bavarian Nordic, Inc.|