A Phase I Study To Evaluate The Antitumor Activity And Safety Of AVX901
HER2 is a protein that is over expressed in 20-30% of breast cancers. It is also found associated with lung, gastric, ovarian, and pancreatic cancers. Although there are existing therapies that can target HER2, most patients will eventually experience progression of their disease even though their cancer continues to express HER2. Therefore, new approaches are needed for treating tumors that express HER2.
This clinical trial will use an investigational cancer vaccine called HER2 VRP or AVX901. The vaccine is based on a virus called Venezuelan equine encephalitis but it has been changed so it cannot cause active infection. Instead, the virus has been changed so it tells the immune system to attack cancer cells which make HER2.
The objectives of the study are to evaluate the safety of immunization with HER2 VRP in patients with advanced or metastatic malignancies that express HER2, and to test whether immunization will causes a strong immune system attack against the cancer.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||A Phase I Study To Evaluate The Antitumor Activity And Safety Of DUKE-002-VRP(HUHER2-ECD+TM), An Alphaviral Vector Encoding The HER2 Extracellular Domain And Transmembrane Region, In Patient With Locally Advanced Or Metastatic Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Cancers Including Breast Cancer|
- Safety [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]The primary objective of the study is to evaluate the safety of immunization with HER2 ECDTM VRP in patients with advanced or metastatic HER2-expressing malignancies
- Immune response [ Time Frame: 3 months ] [ Designated as safety issue: No ]The secondary objective of the study HER2 specific response by ELISPOT and ELISA.
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
AVX901 at 4 x 108 IU intramuscularly, given every 2 weeks for a total of three doses.
Dosing will consist of AVX901 at 4 x 10E8 IU intramuscularly, given every 2 weeks for a total of three doses.
Other Name: VRP-HER2 ECDTM
Metastatic breast cancer continues to account for more than 400,000 deaths yearly with HER2 positive breast cancers representing approximately one third of cases. Despite the efficacy of trastuzumab in HER2 overexpressing breast cancer, progression of metastatic disease is inevitable. Lapatinib, when combined with capecitabine, improves time to progression in those with trastuzumab resistant disease, but lapatinib resistance also develops in the majority of these patients. HER2 overexpression is also reported in lung, gastric, ovarian, and pancreatic cancers, all of which are also in need of improved treatment options. Because HER2 continues to be expressed in patients with refractory disease, using an immune-targeting approach against HER2 remains a promising strategy. A number of clinical trials have confirmed the ability of vaccines to activate T cell and antibody responses against HER2. We propose using a propagation-defective, single-cycle, RNA replicon vector system that expresses HER2 as an antigen-specific cancer vaccine in a Phase I clinical trial in patients with advanced or metastatic malignancies expressing HER2. The vaccine was prepared from an attenuated strain of an alphavirus in which 3 of the 7 viral genes were removed and replaced with a HER2 gene to create a self-amplifying RNA (replicon) that expresses large amounts of HER2. The HER2 gene used includes the extracellular domain (ECD) and transmembrane (TM) regions of HER2 but not the ICD region. The HER2 ECDTM replicon is packaged into virus-like replicon particles (VRP) by providing the alphavirus structural proteins from separate RNA molecules. When VRP are used for immunization, the VRP infect individual cells and the replicon expresses HER2 which then induces an immune response.
The primary objective of the study is to evaluate the safety of immunization with HER2 ECDTM VRP in patients with advanced or metastatic HER2-expressing malignancies. The study will also monitor immune responses to HER2. Preliminary data on tumor response rate will also be collected.
|Contact: Shawna Savageemail@example.com|
|Contact: Amy Hobeika, PhDfirstname.lastname@example.org|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Shawna Savage 919-684-6342 email@example.com|
|Principal Investigator: Michael Morse, MD|
|Principal Investigator:||Michael Morse, MD||Duke University|
|Study Director:||H. Kim Lyerly, MD||Duke University|