Topical Retinoids for Chemoprevention of Melanoma

描述（由申请人提供）：恶性黑色素瘤的发病率以每年2.7%的速度增长，而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一种含有维甲酸（ATRA）的外用制剂商业化，用于患有发育不良痣且发展为恶性黑色素瘤风险较高的受试者。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引起的皮肤刺激。一期研究表明，生物聚合物壳聚糖可作为ATRA的局部递送系统。在这项II期SBIR研究中，我们建议：(1)根据我们的IND 60,073规范含有ATRA/壳聚糖递送系统的外用制剂，(2)根据FDA 21 CFR第58部分测试该制剂在啮齿动物和非啮齿动物物种中的长期毒性和刺激性，(3)确定6个月外用ATRA/壳聚糖是否会导致发育不良痣的显著临床改善，和/或发育不良等级降低，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后的临床和组织学评估，开展了一项涉及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.