Episcleral Chemotherapy as Salvage Therapy for Eyes with Retinoblastoma

巩膜外层化疗作为视网膜母细胞瘤眼睛的挽救疗法

• 批准号: 7925851
• 负责人: Ricardo A Carvalho
• 金额: $ 276.95万
• 依托单位: TARGETED THERAPY TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-27 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925851
• 关键词: Award; Blood Circulation; Bone Marrow Suppression; Carboplatin; Child; Choroid; Chronic; Clinical; Clinical Trials; Devices; Diffuse; Diffusion; Disease; Disease remission; Drug Formulations; Drug Kinetics; Enrollment; Eye; Funding; Grant; Health Care Costs; Histopathology; Intraocular retinoblastoma; Los Angeles; Malignant Childhood Neoplasm; Malignant Neoplasms; Marketing; Maximum Tolerated Dose; Optic Atrophy; Orphan; Outcome; Outcome Measure; Patients; Peripheral; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Posterior eyeball segment structure; Qualifying; Radiation therapy; Recurrence; Renal function; Request for Applications; Retina; Retinoblastoma; Safety; Salvage Therapy; Serum; Silicones; Structure of lamina episcleralis; Surface; System; Therapeutic Agents; Tissues; Topotecan; Toxic effect; base; chemotherapy; hearing impairment; improved; leukemia; novel; phase 1 study; phase 2 study; primary outcome; public health relevance; response; secondary outcome; tumor

DESCRIPTION (provided by applicant): Retinoblastoma is a rare intraocular cancer in children treated either by removing the eye or giving the child systemic chemotherapy with its attendant toxicity and marginal efficacy for sustained intraocular remission. The episcleral device is a novel system for facilitating the sustained local delivery of therapeutic agents, including chemotherapeutic formulations, directly to the interior of the eye while sequestering these agents from washout to peripheral circulation and protecting sensitive periocular tissues. Inside the impermeable silicone episcleral device, the contents of the drug reservoir are maintained in direct contact with a broad expanse of the outer surface of the eye wall (the episclera), greatly facilitating the net passive unidirectional transscleral diffusion of these agents to the intraocular tumor inside the eye. Delivery from the episcleral exoplant may be sustained for months to years depending on the drug formulation. This RC3 grant requests funding to support clinical trials in patients with advanced unilateral retinoblastoma prescheduled to have an eye surgically removed. Thus this trial will be salvage therapy. Demonstration of safety, tolerability and efficacy will allow 3T Ophthalmics to rapidly bring to market a paradigm change for the treatment of chronic intraocular diseases. PUBLIC HEALTH RELEVANCE: This application requests funding to support the efforts of 3T Ophthalmics to complete clinical trials of their episcleral delivery system that provides therapeutic agents by sequestered passive diffusion across the surface of the eye. Specifically funds requested will support Phase I and Phase II clinical trials of episcleral formulations of carboplatin and topotecan in eyes of children with advanced intraocular retinoblastoma (all IND enabling studies and clinical supplies are covered by a recently awarded NCI-RAID grant). If local targeted episcleral delivery of these agents can safely reduce or eliminate the need for enucleation, systemic chemotherapy, and radiotherapy in eyes with this orphan childhood cancer, then this approach has potential to significantly improve the delivery and reduce the costs of health-care in retinoblastoma as well in many other ophthalmic diseases.

描述（由申请人提供）：视网膜母细胞瘤是一种罕见的儿童眼内癌症，通过摘除眼睛或给予儿童全身化疗治疗，伴随毒性和持续眼内缓解的边际疗效。巩膜外装置是一种新型系统，用于促进治疗剂（包括化学治疗制剂）直接持续局部递送至眼睛内部，同时隔离这些药剂以免冲洗至外周循环并保护敏感的眼周组织。在不可渗透的硅树脂巩膜外装置内，药物储存器的内容物保持与眼壁的外表面（巩膜外膜）的广阔区域直接接触，极大地促进了这些药剂向眼内的眼内肿瘤的净被动单向经巩膜扩散。从巩膜外植体的递送可持续数月至数年，这取决于药物制剂。该RC 3赠款要求提供资金，以支持晚期单侧视网膜母细胞瘤患者的临床试验，这些患者需要通过手术切除眼睛。因此，本试验将是挽救治疗。安全性、耐受性和有效性的证明将使3 T Ophthalalocyte能够迅速将治疗慢性眼内疾病的范式转变推向市场。 公共卫生相关性：该申请要求提供资金，以支持3 T眼科完成其巩膜外给药系统的临床试验，该系统通过在眼表面隔离被动扩散提供治疗剂。具体而言，申请的资金将用于支持卡铂和托泊替康的巩膜外制剂在晚期眼内视网膜母细胞瘤儿童眼中的I期和II期临床试验（所有IND使能研究和临床供应均由最近授予的NCI-RAID补助金支付）。如果这些药物的局部靶向巩膜外递送可以安全地减少或消除患有这种孤儿儿童癌症的眼睛对眼球摘除术、全身化疗和放疗的需要，那么这种方法有可能显著改善视网膜母细胞瘤以及许多其他眼科疾病的递送并降低医疗保健成本。