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

描述(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，五年生存率为1%，是所有胃肠道恶性肿瘤中最糟糕的。胰腺癌预后较差的原因与早期未能诊断，以及胰腺癌对常规化疗和放射治疗无反应有关。吉西他滨已经成为治疗晚期胰腺癌的标准治疗方法；然而，据报道，吉西他滨的平均生存期只有5.6个月。我们的研究小组发现了一种名为阿片类生长因子(OGF)的新型生物疗法，它可以在体外、动物和人体中抑制胰腺癌的生长。OGF的1期研究已经完成，并对最大耐受剂量、安全性和毒性进行了评估。目前，第二阶段试验正在进行中，以研究OGF单一疗法对那些对标准治疗没有反应的人的疗效。我们的基础科学实验室最近的实验表明，当OGF与吉西他滨联合使用时，在抑制癌症方面具有显著的相加益处。此外，接受联合治疗的动物比单独接受吉西他滨治疗的动物更健康，这表明OGF可能对化疗毒性有保护作用。推测OGF联合吉西他滨治疗不能切除的胰腺癌是安全的。为了验证这一假设，22名符合条件的初治胰腺癌患者将接受标准剂量的吉西他滨治疗。与此同时，OGF将从150g/kg开始每周给药，并增加到最大耐受量250g/kg，以确定以下具体目标：1)评估OGF生物治疗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了两种药物的药代动力学；以及3)研究联合治疗对肿瘤大小、患者生存时间和疾病进展时间的影响。我们研究团队的长期目标包括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存活率。公共卫生相关性：在这项提案中，一种名为OGF的新型自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无法手术的未经治疗的胰腺癌患者中进行测试。OGF是一种新发现的抑制胰腺癌生长的药物，研究表明，与吉西他滨一起服用可能会有更好的效果。静脉注射将每周进行一次，随后将进行血液测试和CT扫描，以确保安全和有效。

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.