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

有机生长因子

• 批准号: 7688483
• 负责人: Jill P Smith
• 金额: $ 7.76万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-17 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7688483
• 关键词: Adverse effects; Animals; Basic Science; Biological Response Modifier Therapy; Blood Tests; Cancer Etiology; Cancer Patient; Cell Culture Techniques; Cessation of life; Chronic Phase; Clinical; Combined Modality Therapy; Data; Diagnosis; Disease; Disease Progression; Dose; Drug Administration Routes; Enkephalins; Excision; Failure; Goals; Grant; Growth; Growth Factor; Hospice Care; Human; In Vitro; Individual; Infusion procedures; Intravenous; Laboratories; Malignant Neoplasms; Malignant neoplasm of pancreas; Maximum Tolerated Dose; Nature; New Agents; Nude Mice; Operative Surgical Procedures; Opioid; Orphan Drugs; Patients; Peptides; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Radiation therapy; Reporting; Research; Role; Safety; Solid Neoplasm; Staging; Survival Rate; Testing; Time; Toxic effect; Toxicity due to chemotherapy; Translations; Treatment Protocols; United States; United States National Institutes of Health; Unresectable; Veins; X-Ray Computed Tomography; Xenograft procedure; advanced disease; anticancer research; cancer cell; cancer diagnosis; chemotherapy; clinical practice; efficacy testing; gastrointestinal; gemcitabine; hospice environment; human subject; improved; novel; outcome forecast; pancreatic neoplasm; pre-clinical; programs; protective effect; public health relevance; research study; response; standard care; standard of care; tumor; tumor growth

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.

描述（由适用提供）：胰腺癌是美国与癌症相关死亡的第四个主要原因，中位生存期为3-6个月，五年生存率为1％，使其在所有胃肠道恶性肿瘤中的情况差。预后不良的原因与未能在早期诊断该癌症的情况以及胰腺癌对常规化学疗法和放射治疗的反应无反应症有关。吉西他滨已成为晚期胰腺癌治疗的护理标准。但是，仅在5.6个月的时间内报道了吉西他滨的平均生存期。我们的研究团队发现了一种称为阿片类药物生长因子（OGF）的新型生物疗法，该生物疗法在体外，动物和人类受试者中抑制胰腺癌的生长。对OGF的1期研究已经完成，并评估了最大耐受剂量，安全性和毒性。目前，正在进行2阶段试验，以研究OGF单药治疗在未反应标准治疗的人中的有效性。我们的基础科学实验室的最新实验表明，当OGF与吉西他滨结合使用时，癌症抑制作用显着。此外，接受联合制度的动物比单独接受吉西他滨治疗的动物更健康，这表明OGF对化学疗法毒性具有保护作用。假设OGF可以安全地与吉西他滨结合给无法切除的胰腺癌患者。为了检验这一假设22符合条件的胰腺癌患者，预计将用标准剂量的吉西他滨治疗。同时，每周从150？g/kg开始每周施用OGF，并增加到最大耐受剂量为250？g/kg，以确定以下特定目的：1）评估OGF生物疗法和吉西宾的安全性和毒性； 2）确定联合疗法是否会改变任何一种药物的药物； 3）研究联合疗法对肿瘤大小，患者生存和疾病进展的时间的有效性。我们研究团队的长期目标涉及将基础科学实验室的新发现转化为临床实践，其最终目标是改善这种毁灭性疾病的患者的生存。公共卫生相关性：在此提案中，在未经治疗的胰腺癌患者中，将测试一种称为OGF的新天然生物疗法的安全性和有效性，它将通过标准的化学疗法（吉西他滨）进行测试。 OGF是一种发现抑制胰腺癌生长的新药物，研究在用吉西他滨给出时可能会更好地结果。每周静脉和血液测试和CT扫描将进行安全和反应，将进行输注。