4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN): A Phase II Clinica

描述（由申请人提供）：本研究项目的主要目标是在II期临床试验中评估4-去甲基-4-胆固醇氧羰基彭洛美定（dm - chocc - pen），一种多氯代碳酸胆固醇作为晚期癌症患者的抗癌药物。在临床前研究中，dm - chocc - pen与颅内（IC）植入的人类胶质瘤和乳腺癌异种移植和黑色素瘤小鼠模型相比，在小鼠的长期生存中产生了完全缓解。在最近完成的I期临床试验（包括中枢神经系统受累的患者）中，该药物被证明是无神经毒性的。一些患者-肉瘤，GBM，乳腺癌（中枢神经系统病变）已经表现出PFS[6-18]。一个（肉瘤扩散到正弦）有NED × 12+ mos。未观察到肾、肺和血液系统的副作用；剂量限制效应是肝脏胆红素升高。完整的药代动力学研究/参数进行了回顾。临床产品为乳剂，冷藏稳定性为1.5年。该包装已通过IRBs和FDA的审查- IND 68,876。目标将包括：1)启动一项II期试验，dm - chocc - pen IV给药给晚期或复发癌症患者（可接受+/-中枢神经系统受损伤），并验证建议剂量是可接受的，监测药理学和毒性。2)根据RECIST指南监测肿瘤对dm - chocc - pen的每次成像/检查的反应。3)以电子方式存储/分析毒性、反应和肿瘤-器官关系的临床数据。4)在可能的情况下继续储存治疗前后患者的肿瘤组织，并检测肿瘤药物/代谢物含量和生物标志物；5)为dm - chocc - pen在特定肿瘤类型患者中的二期（双药）或三期（单药）试验准备FDA报告。

DESCRIPTION (provided by applicant): The principal goal of this research project will be to evaluate 4-demethyl-4- cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), a polychlorinated cholesterol carbonate as anticancer therapy for patients with advanced cancer in a Phase II clinical trial. During pre-clinical studies DM-CHOC-PEN produced complete remissions with long term survival vs. intracranially (IC) implanted human gliomas and breast cancer xenograft and melanoma murine models in mice. In the recently completed Phase I clinical trial (that included patients with CNS involvement), the drug proved to be non-neurotoxic. Several patients - sarcoma, GBM, breast cancer (CNS lesions) have demonstrated PFS > 6-18 mos. and one (sarcoma spread to the sine) has NED x 12+ mos. Renal, pulmonary and hematological side effects were not observed; dose limiting effect was hepatic - elevated bilirubin. Complete pharmacokinetic studies/parameters are reviewed. The clinical product is an emulsion with stability under refrigeration - 1.5 yrs. The package has been reviewed by IRBs and FDA - IND 68,876. The aims will include: 1) Initiate a Phase II trial with DM-CHOC-PEN administered IV to patients with advanced or recurrent cancer (+/- CNS involvement acceptable) and verify that the proposed dose is acceptable, monitor pharmacodynamics and toxicities. 2) Monitor tumor responses to DM-CHOC-PEN per imaging/examinations using RECIST guidelines. 3) Electronically store/analyze clinical data for toxicity, responses and tumor-organ relationships. 4) Continue to bank tumor tissue from pre- and post-treated patients when possible and assay tumor - drug/metabolite content and bio-markers; store blood samples for future studies, i.e. Caris Target Now, etc. 5) Prepare a FDA presentation for subsequent Phase II (binary drug) or III (single drug) trials with DM-CHOC-PEN in patients with specific tumor types.