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Chemoprevention of Oral Cancer with BBIC

使用 BBIC 化学预防口腔癌

基本信息

批准号：
7278200
负责人：
FRANK L. MEYSKENS
金额：
$ 43.94万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-03-14 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7278200
关键词：
Adherence Adverse effects Appendix Attention Biochemical Biological Models Biopsy Bowman-Birk inhibitor Cancer Control Categories Cells Characteristics Chemoprevention Chemopreventive Agent Clinical Clinical Trials Data Monitoring Committees Data Development Dietary Alcohol Disease regression Double-Blind Method Effectiveness End Point Endopeptidases Enrollment Epidermal Growth Factor Receptor Evaluation Factor Analysis Glycine max Goals Head and Neck Cancer Head and neck structure Histologic Human Immunohistochemistry Individual Lesion Leukoplakia Longitudinal Studies Malignant Neoplasms Measurement Measures Modality Molecular Monitor Numbers Oncogenes Oral Examination Oral Leukoplakia Oral cavity Oral mucous membrane structure Patients Peptide Hydrolases Pharmaceutical Preparations Phase Phase I Clinical Trials Photography Placebo Control Prevention Process Property Protease Inhibitor Protein p53 Proteins Questionnaires Randomized Rate Reporting Research Research Personnel Retinoic Acid Receptor Retinoids Risk Factors Risk Reduction Role Safety Second Primary Neoplasms Serum Serum Proteins Soybeans Standards of Weights and Measures System TP53 gene Therapeutic Tissues Tobacco Toxic effect Toxicology Work base carcinogenesis falls human RARB protein indexing malignant mouth neoplasm mutant pre-clinical prevent programs protective effect prototype response

项目摘要

DESCRIPTION (provided by applicant): The long term objective of this proposal is to determine whether Bowman-Birk Inhibitor (BBI) Concentrate (C), a protease inhibitor extracted from soybeans, can cause regression of oral leukoplakia and whether certain candidate intermediate marker endpoints can predict response by serving as a surrogate for oral leukoplakia. The ultimate goal of this research is to prevent human cancer. The specific aims are: (1) To conduct a placebo-controlled, double-blind and randomized 6 month phase lib cancer control chemoprevention trial of BBIC in patients with oral leukoplakia. (a) To determine the clinical and histologic response rate of oral leukoplakia to BBIC. (b) To serially measure the effect of BBIC on intermediate marker endpoints (IME). 1) In oral mucosal cells the level of proteolytic activity (PA) and levels of erb-B2 (neu), retinoic acid receptor beta (RAR-beta), bcl-2, and mutant p53 protein will be measured. 2) In tissue biopsies of oral leukoplakia lesions the latter four proteins above will also be measured by immunohistochemistry. 3) In serum, the levels of the protein, neu, will be serially measured. (c) To correlate the clinical and histologic responses of oral leukoplakia to the effect on cellular levels of PA, erb-B2 (neu), RAR-beta, bcl-2, and mutant p53 expression, and serum levels of neu. (d) To determine the individual and group side-effects to BBIC. (2) To follow long term (one year) those patients who achieve a PR or CR afterthe initial 6 months trial Based on the phase Ila and early phase lib results we estimate that about 25-35% of patients completing the 6 months of BBIC will fall in this category. The same parameters outlined for specific aim 1 will be measured. Particular attention will be paid to adherence and toxicity as we eventually wish to use BBIC in the long term setting of second malignancy prevention. All aspects of these phase II IME trials will be carefully monitored for compliance, safety, and toxicity by continuous local evaluation by our NCI-approved Data Safety and Monitoring Board (DSMB) and in concert with the NCI. The results from these studies should provide a substantial biologic and therapeutic rationale for a large Phase III randomized risk reduction trial of head and neck cancer as well as provide impetus for further exploration of these non-toxic group of compounds as chemopreventive agents in humans.

描述（由申请方提供）：本提案的长期目标是确定Bowman-Birk抑制剂（BBI）浓缩物（C）（一种从大豆中提取的蛋白酶抑制剂）是否可导致口腔白斑消退，以及某些候选中间标志物终点是否可通过作为口腔白斑的替代品来预测缓解。这项研究的最终目的是预防人类癌症。具体目标是： (1)在口腔白斑患者中进行BBIC的安慰剂对照、双盲和随机6个月IIb期癌症对照化学预防试验。 (a)探讨BBIC治疗口腔白斑的临床和组织学疗效。 (b)连续测量BBIC对中间标志物终点（IME）的影响。 1)在口腔粘膜细胞中，将测量蛋白水解活性（PA）水平和erb-B2（neu）、视黄酸受体β（RAR-β）、bcl-2和突变型p53蛋白水平。 2)在口腔白斑病变的组织活检中，上述后四种蛋白质也将被检测。通过免疫组织化学测量。 3)在血清中，将连续测量蛋白neu的水平。 (c)将口腔白斑的临床和组织学反应与PA、erb-B2（neu）、RAR-β、bcl-2和突变型p53表达的细胞水平以及neu的血清水平的影响相关联。 (d)确定BBIC的个体和群体副作用。 (2)长期（1年）随访在最初6个月试验后达到PR或CR的患者根据IIa期和IIb期早期的结果，我们估计约25-35%的患者完成6个月的BBIC将属于这一类。将测量具体目标1所列的相同参数。我们将特别关注依从性和毒性，因为我们最终希望在第二次恶性肿瘤预防的长期环境中使用BBIC。这些II期IME试验的所有方面将通过我们的NCI批准的数据安全和监测委员会（DSMB）并与NCI合作进行持续的当地评价，仔细监测依从性、安全性和毒性。这些研究的结果应该为头颈癌的大型III期随机风险降低试验提供实质性的生物学和治疗原理，并为进一步探索这些无毒化合物作为人类化学预防剂提供动力。