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

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN)：II 期临床

基本信息

批准号：
8523101
负责人：
Lee ROY MORGAN
金额：
$ 63.86万
依托单位：
DEKK-TEC, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8523101
关键词：
Advanced Malignant Neoplasm Adverse effects Animals Autophagocytosis Back Bilirubin Biological Assay Blood - brain barrier anatomy Blood Circulation Blood specimen Breast Melanoma Carbamates Carbonates Carrier Proteins Cell Death Central Nervous System Diseases Central Nervous System Neoplasms Cholesterol Clinical Clinical Data DNA Alkylation Development Disease remission Disseminated Malignant Neoplasm Dose Dose-Limiting Drug Formulations Drug Kinetics Emulsions Enrollment Evaluation Functional disorder Future Glioblastoma Glioma Goals Guanine Guidelines Hepatic Human Image Implant Incidence Institutional Review Boards Intracranial Neoplasms Kidney Lesion Long-Term Survivors Lung Malignant Neoplasms Metastatic Neoplasm to the Liver Metastatic malignant neoplasm to brain Mitochondria Modeling Monitor Mus Nervous system structure Organ P-Glycoprotein Patients Performance Pharmaceutical Preparations Pharmacodynamics Phase Phase I Clinical Trials Phase II Clinical Trials Property Quality of life Reactive Oxygen Species Recurrent Malignant Neoplasm Recycling Refrigeration Reporting Research Project Grants Series Spinal Spinal Cord Stress Time Toxic effect Tumor Tissue U251 Xenograft Model Xenograft procedure cancer therapy design irritation malignant breast neoplasm melanoma member mouse model neurotoxicity novel outcome forecast phase 1 study preclinical study psychologic public health relevance pyridine response sarcoma tumor

项目摘要

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.

描述（由申请人提供）：该研究项目的主要目标是评估 4-去甲基-4-胆固醇氧羰基喷氯米定 (DM-CHOC-PEN)，一种多氯胆固醇碳酸盐作为晚期癌症患者的 II 期临床抗癌疗法审判。在临床前研究中，与颅内 (IC) 植入的人类神经胶质瘤、乳腺癌异种移植和黑色素瘤小鼠模型相比，DM-CHOC-PEN 实现了完全缓解，并具有长期存活率。在最近完成的一期临床试验（包括中枢神经系统受累患者）中，该药物被证明没有神经毒性。一些肉瘤、GBM、乳腺癌（中枢神经系统病变）患者已证明 PFS > 6-18 个月。一个（肉瘤扩散到正弦）具有 NED x 12+ mos。未观察到肾、肺和血液学副作用；剂量限制作用是肝脏-胆红素升高。审查完整的药代动力学研究/参数。临床产品是一种乳剂，在冷藏条件下可保持 1.5 年稳定性。该包装已通过 IRB 和 FDA 审查 - IND 68,876。目标包括： 1) 启动一项 II 期试验，对晚期或复发性癌症患者（可接受+/- CNS 累及）静脉注射 DM-CHOC-PEN，并验证提议的剂量是否可接受，监测药效学和毒性。 2) 使用 RECIST 指南监测每次成像/检查时肿瘤对 DM-CHOC-PEN 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和治疗后患者的肿瘤组织，并测定肿瘤药物/代谢物含量和生物标志物；储存血液样本以供未来研究，即 Caris Target Now 等。 5) 为后续针对特定肿瘤类型患者进行 DM-CHOC-PEN 的 II 期（二元药物）或 III 期（单一药物）试验准备 FDA 演示文稿。