Research Project
7596429
DESCRIPTION (provided by applicant): The long-term objective of this proposal is to develop a safe and efficacious therapy for the treatment of ovarian cancer, the most lethal of gynecological malignancies in women with an estimated prevalence of 167,000 women in the United States. Nearly 55 to 75% of women develop recurrent ovarian cancer within two years after the first line of treatments, which underscores the need for new and more potent therapy for this rare disease. The investigators propose to develop a novel interleukin-12 (IL-12) based immunotherapeutic, EGEN-001, for the treatment of recurrent ovarian cancer. EGEN-001 is composed of an IL-12 expression plasmid and a synthetic gene delivery polymer (PEG-PEI-Cholesterol) that is designed to promote IL-12 gene transfer at tumor site after intra-abdominal administration. IL-12 is a potent anti-cancer cytokine that inhibits cancer growth and metastases by activation of the immune system. Enhancing a patient's ability to fight off ovarian cancer by sustained IL-12 delivery alongside with standard chemotherapy offers a new paradigm for safer and more effective treatment of this rare disease. The specific aim of this proposal is to test the safety and efficacy of EGEN-001 treatment alongside with standard chemotherapy in women with recurrent ovarian cancer. Since EGEN-001 has not been previously tested in humans, its safety as monotherapy will first be established. The maximum tolerated dose of EGEN-001 in women with chemotherapy-resistant advanced recurrent ovarian cancer will be determined by a dose-escalation study. After demonstration of the monotherapy safety and tolerability, EGEN-001 will be co-administered with carboplatin/paclitaxel to determine its safe dose in the combination therapy. The treatment safety will be assessed from vital signs, hematology, clinical chemistries, urinalysis, ECG parameters, and chest X-Ray analyses. Finally, the preliminary efficacy of the maximum tolerated dose of EGEN-001 administered with carboplatin/paclitaxel will be assessed in a larger platinum-sensitive patient population. Treatment efficacy will be assessed by tumor regression, time to progression of disease and CA-125 levels. Favorable results from the above studies would lay the foundation for testing EGEN-001/chemotherapy combination in a larger patient population (Phase 3) eventually leading up to product commercialization. The proposed research is anticipated to result in a safer and more efficacious treatment modality for ovarian cancer due to its ability to enhance the body's natural ability to fight off cancer.
