DOSE ESCALATION TRIAL OF 100AA SYNTHETIC MUCIN PEPTIDE PANCREATIC CANCER

本研究的目的是：1)合成粘蛋白肽疫苗的毒性和安全性。2)为未来的研究建立II期剂量。3)通过PET扫描获得局部晚期胰腺癌muc1接种后肿瘤行为的定性和定量信息。4)局部晚期肿瘤消退的客观证据。5)评估局部晚期患者的无病生存期和所有患者的总生存期。105aa muc1疫苗在胰腺癌、乳腺癌和结肠癌中显示出免疫原性。本研究中使用的100aa MCU-1疫苗与105aa疫苗相似，但经过精炼，不含末端5个氨基酸序列。疫苗注射的最佳剂量和时间表尚不清楚。在这项研究中，佐剂将是SB-AS2，它已证明具有免疫刺激特性。与卡介苗不同的是，在大多数患者中，卡介苗与严重的皮肤毒性有关，包括溃疡，而SB-AS2似乎引起的皮肤毒性要小得多。我们建议在胰腺癌中进行100aa MUC-1肽与SB-AS2混合的I期剂量递增研究，因为目前的治疗方法具有边际效益，并且此类患者可以在伦理上考虑进行研究性治疗。

The objectives of this study will be: 1)The toxicity and safety of the synthetic mucin peptide vaccine. 2)Establishing a phase II dose for future studies. 3)To obtain qualitative and quantitative information on tumor behavior by PET scans in response to MUC-1 vaccination in locally advanced pancreatic cancer. 4)Objective evidence of tumor regression in locally advanced disease. 5)Evaluate the disease free survival in patients with locally advanced disease and overall survival of all patients. The 105aa MUC-1 vaccine has shown immunogenicity in pancreatic, breast and colon cancer. The 100aa MCU-1 vaccine to be used in this study is similar to the 105aa vaccine but has been refined without the terminal five amino acid sequence. The optimum dose and schedule of vaccine administration is not known. In this study the adjuvant will be SB-AS2 which has demonstrated immunostimulant properties. Unlike BCG which is associated with severe skin toxicity including ulceration in the majority of patients, SB-AS2 appears to cause much less skin toxicity. We propose to do a Phase I dose escalation study of the 100aa MUC-1 peptide admixed with SB-AS2, in pancreatic cancer as current therapies are of marginal benefit and such patients can be ethically considered for investigational therapy.