DOSE ESCALATION TRIAL OF 100AA SYNTHETIC MUCIN PEPTIDE PANCREATIC CANCER

本研究的目的是：1)合成粘蛋白多肽疫苗的毒性和安全性。2)建立二期剂量供今后研究之用。3)通过PET扫描获得局部晚期胰腺癌患者接种MUC-1疫苗后肿瘤行为的定性和定量信息。4)局部晚期疾病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 MUC-1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，但经过精制，没有末端五个氨基酸序列。疫苗接种的最佳剂量和时间尚不清楚。在本研究中，佐剂将是具有免疫刺激特性的SB-AS2。与卡介苗不同的是，在大多数患者中，卡介苗会引起严重的皮肤毒性，包括溃疡，而SB-AS2的皮肤毒性似乎要小得多。我们建议在胰腺癌中进行一项100aa MUC-1肽与SB-AS2混合的I期剂量递增研究，因为目前的治疗效果微乎其微，从伦理学的角度来看，这些患者可以被考虑进行研究治疗。

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.