Topical Retinoids for Chemoprevention of Melanoma

描述（由申请人提供）：恶性黑色素瘤的发病率每年增加2.7%，即使大多数其他癌症的发病率正在下降。该项目的长期目标是将含有维甲酸（ATRA）的局部制剂商业化，用于患有发育异常痣的受试者，这些受试者具有发生恶性黑色素瘤的较高风险。然而，ATRA对皮肤有很强的刺激性。几种局部给药系统已被证明可以减少ATRA诱导的皮肤刺激。I期研究表明，生物聚合物壳聚糖作为ATRA的局部给药系统。在本II期SBIR研究中，我们建议：（1）根据我们的IND 60，073标准化含有ATRA/壳聚糖递送系统的局部制剂，（2）根据FDA 21 CFR，第58部分在啮齿动物和非啮齿动物物种中测试制剂的长期毒性和刺激性，（3）确定6个月的局部ATRA/壳聚糖是否会导致发育异常痣的显著临床改善，和/或发育异常等级的降低，和/或增殖生物标志物表达的变化，通过使用基于互联网的随机化、电子数据采集、协调和监测以及研究前和研究后的临床和组织学评估进行涉及16名发育不良痣受试者的多中心对照临床试验。

DESCRIPTION (provided by applicant): Malignant melanoma's incidence is increasing by 2.7% annually even as most other cancers are experiencing a decline in incidence. The long-term objective of this project is to commercialize a topical formulation containing retinoic acid (ATRA) for subjects with dysplastic nevi at a higher risk of developing malignant melanoma. However, ATRA is highly irritating to the skin. Several topical delivery systems have been shown to reduce ATRA-induced skin irritation. Phase I studies have shown that the biopolymer chitosan acts as a topical delivery system for ATRA. In this Phase II SBIR study we propose to: (1) standardize the topical formulation containing the ATRA/chitosan delivery system according to our IND 60,073, (2) test the long-term toxicity and irritation of the formulation in both rodents and non-rodents species according to FDA 21 CFR, Part 58, (3) determine whether 6 months of topical ATRA/chitosan will result in a significant clinical improvement of dysplastic nevi, and/or a decrease in the dysplasia grade, and/or a change in the expression of proliferation biomarkers, by performing a multicenter controlled clinical trial involving 16 dysplastic nevi subjects using Internet-based randomization, electronic data capture, coordination and monitoring, and pre and post study clinical and histological assessment.