OGF & Gemcitabine: A Novel Treatment for Pancreatic Cancer: Phase I Study

描述（由申请人提供）：胰腺癌是美国癌症相关死亡的第四大原因，中位生存期为3-6个月，5年生存率为1%，是所有胃肠道恶性肿瘤中最严重的。预后不良的原因与未能在早期阶段诊断这种癌症以及胰腺癌对常规化疗和放射治疗无反应有关。吉西他滨已成为治疗晚期胰腺癌的标准治疗;然而，吉西他滨的平均生存期仅为5.6个月。我们的研究团队发现了一种名为阿片样生长因子（OGF）的新型生物疗法，可在体外、动物和人类受试者中抑制胰腺癌的生长。已经完成了OGF的I期研究，并评估了最大耐受剂量、安全性和毒性。目前正在进行一项2期试验，以研究OGF单药治疗对标准治疗无反应的患者的疗效。我们基础科学实验室的最新实验表明，当OGF与吉西他滨联合使用时，在癌症抑制方面具有显著的附加益处。此外，接受联合方案的动物比单独用吉西他滨治疗的动物更健康，这可能表明OGF对化疗毒性的保护作用。据推测，OGF可以安全地与吉西他滨联合施用于患有不可切除的胰腺癌的个体。为了检验这一假设，将对22例合格的胰腺癌初治患者进行标准剂量吉西他滨的前瞻性治疗。同时，OGF将每周给药一次，从150？g/kg，并增加至最大耐受剂量250？g/kg，以确定以下具体目的：1）评价OGF生物疗法和吉西他滨联合治疗的安全性和毒性; 2）确定联合治疗是否改变任一药物的药代动力学;和3）研究联合治疗的功效对肿瘤大小、患者生存期和疾病进展时间的影响。我们研究团队的长期目标是将基础科学实验室的新发现转化为临床实践，最终目标是提高这种毁灭性疾病患者的生存率。公共卫生相关性：在这项提案中，一种名为OGF的新天然生物疗法的安全性和有效性将与标准化疗吉西他滨一起在未经治疗的胰腺癌患者中进行测试，这些患者不适合手术。OGF是一种新发现的抑制胰腺癌生长的药物，研究表明与吉西他滨联合使用可能会有更好的效果。每周通过静脉输注，随后进行血液检查和CT扫描，以确定安全性和反应。

DESCRIPTION (provided by applicant): Pancreatic cancer is the 4th leading cause of cancer-related deaths in the United States with a median survival of 3-6 months and a five-year survival rate of 1% making it the worse of all gastrointestinal malignancies. The reason for the poor prognosis is related to failure to diagnose this cancer in early stages and the unresponsiveness of pancreatic cancer to conventional chemotherapy and radiation therapy. Gemcitabine has become the standard of care in treatment of advanced pancreatic cancer; however, the mean survival with gemcitabine is reported at only 5.6 months. Our research team has discovered a novel biotherapy called Opioid Growth Factor (OGF) that inhibits growth of pancreatic cancer in vitro, in animals, and in human subjects. A Phase 1 study with OGF has been completed and the maximum tolerated dose, safety and toxicity evaluated. Currently a Phase 2 trial is in progress to study the efficacy of OGF monotherapy in those who have not responded to standard treatment. Recent experiments from our basic science laboratories indicate a marked additive benefit in cancer inhibition when OGF is combined with gemcitabine. Additionally, animals receiving the combination regime were healthier than those treated with gemcitabine alone suggesting perhaps a protective effect of OGF to chemotherapy toxicity. It is hypothesized that OGF may be safely administered in combination with gemcitabine to individuals with unresectable pancreatic cancer. In order to test this hypothesis 22 eligible na¿ve patients with pancreatic cancer will be prospectively treated with standard doses of gemcitabine. Concomitantly, OGF will be administered weekly starting at 150 ?g/kg and increasing to the Maximum tolerated dose of 250 ?g/kg in order to determine the following specific aims: 1) evaluate the safety and toxicity of the combination of OGF biotherapy and gemcitabine; 2) determine whether the combination therapy alters the pharmakokinetics of either agent; and 3) study the efficacy of combination therapy on tumor size, patient survival, and time to progression of disease. The long-term goal of our research team involves translation of novel discoveries from the basic science laboratory into clinical practice with the ultimate goal of improving survival of patients with this devastating disease. PUBLIC HEALTH RELEVANCE: In this proposal the safety and efficacy of a new natural biotherapy called OGF will be tested with standard chemotherapy, gemcitabine, in untreated patients with pancreatic cancer not amenable to surgery. OGF is a new agent discovered to inhibit growth of pancreatic cancer and research shows possibly better results when given with gemcitabine. Infusions will be given by the vein weekly and blood tests and CT scans followed for safety and response.