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

有机生长因子

• 批准号: 7589518
• 负责人: Jill P Smith
• 金额: $ 7.71万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7589518
• 关键词: Adverse effects; Animals; Basic Science; Biological Response Modifier Therapy; Blood Tests; Cancer Etiology; Cancer Patient; Caring; Cessation of life; Chronic Phase; Clinical; Combined Modality Therapy; Cultured Cells; Data; Diagnosis; Disease; Disease Progression; Dose; End Point; Enkephalins; Excision; Failure; Goals; Grant; Growth; Growth Factor; Hospice Care; Human; In Vitro; Individual; Infusion procedures; Intravenous Route of Drug Administration; 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; Public Health; Radiation therapy; Reporting; Research; Role; Safety; Solid Neoplasm; Staging; Standards of Weights and Measures; Survival Rate; Testing; Time; Toxic effect; Toxicity due to chemotherapy; Translations; Treatment Protocols; United States; United States Food and Drug Administration; United States National Institutes of Health; Unresectable; Veins; X-Ray Computed Tomography; Xenograft procedure; anticancer research; cancer cell; cancer diagnosis; chemotherapy; day; gastrointestinal; gemcitabine; hospice environment; human subject; improved; novel; outcome forecast; pancreatic neoplasm; pre-clinical; programs; protective effect; research study; response; size; 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差的。预后不良的原因与胰腺癌早期诊断失败以及对常规化疗和放疗无反应有关。吉西他滨已经成为晚期胰腺癌治疗的标准；然而，吉西他滨的平均生存期仅为5.6个月。我们的研究小组发现了一种叫做阿片生长因子（OGF）的新型生物疗法，它可以在体外、动物和人类体内抑制胰腺癌的生长。OGF的一期研究已经完成，并对最大耐受剂量、安全性和毒性进行了评估。目前正在进行一项2期试验，以研究OGF单药治疗对标准治疗无效的患者的疗效。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，在癌症抑制方面具有显著的附加效益。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，这可能表明OGF对化疗毒性有保护作用。假设OGF与吉西他滨联合应用于无法切除的胰腺癌患者是安全的。为了验证这一假设，22名符合条件的未出生的胰腺癌患者将接受标准剂量的吉西他滨治疗。同时，OGF将从150 ？g/kg，并逐渐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生物疗法联合吉西他滨的安全性和毒性；2)确定联合治疗是否改变任一药物的药代动力学；3)研究联合治疗对肿瘤大小、患者生存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，最终目标是提高患有这种毁灭性疾病的患者的生存率。公共卫生相关性：在本提案中，一种名为OGF的新型天然生物疗法将与标准化疗吉西他滨一起，在未经治疗的不能手术的胰腺癌患者中进行安全性和有效性测试。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联合使用可能效果更好。每周将通过静脉输注，然后进行血液检查和CT扫描，以确定安全性和反应。