Anticancer Drug Development for Childhood Cancers

儿童癌症的抗癌药物开发

• 批准号: 7969774
• 负责人: Frank Balis
• 金额: $ 112.79万
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7969774
• 关键词: ABT-751; Address; Adjuvant; Angiogenesis Inhibitors; Antineoplastic Agents; Biological Assay; Cancer Center; Cancer Therapy Evaluation Program; Central Nervous System Agents; Characteristics; Child; Childhood; Clinical; Clinical Trials; Conduct Clinical Trials; Cytotoxic agent; Data; Development; Disease; Dose; Drug Delivery Systems; Drug Industry; Drug Kinetics; Enrollment; Ensure; Extramural Activities; Foxes; Funding; Industry; Inherited; Institution; Ixabepilone; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Monoclonal Antibodies; Movement; Neuroblastoma; Neurofibromatoses; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacology; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Positron-Emission Tomography; Predisposition; Research Personnel; Schedule; Syndrome; Tariquidar; Testing; Therapeutic; Therapeutic Uses; Tissue Microarray; Toxic effect; Work; base; cancer genetics; design; drug development; experience; interest; medullary thyroid carcinoma; member; novel; pre-clinical; programs; tool; tumor

The Pharmacology & Experimental Therapeutics (PET) Section focuses on the selection and clinical development of new anticancer drugs for the treatment of childhood cancers, neurofibromatosis (led by Dr. Brigitte Widemann) and cancers that occur in children with genetic cancer predisposition syndromes (Dr. Widemann). The Section has an active clinical trials program to study the toxicity, activity, pharmacokinetics and pharmacodynamics of these agents in children. Clinical trials are performed as single institution studies or collaboratively with other children's cancer centers or cooperative groups. A variety of agents are studied, including molecularly targeted drugs such as vandetanib and R1507, cytotoxic drugs such as trabectedin, antiangiogenic agents such as cediranib, monoclonal antibodies and drugs that modulate the therapeutic or toxic effects of anticancer drugs such as olaparib, talabostat and tariquidar. The Section works with the Cancer Therapy Evaluation Program and the pharmaceutical industry to ensure that promising new drugs are studied in children. The Section is a non-funded member of the COG Phase1/Pilot Consortium and COG. This has allowed the movement of agents studied in phase I trials in the Section (e.g., ABT-751, ixabepilone) into phase II trials in the cooperative groups. For example, the phase I trial of ABT-751 led by Dr. Elizabeth Fox evaluated two dosing schedules and enrolled a total of 76 patients, including 50 patients with neuroblastoma. The preliminary data suggesting that the drug had clinical activity in neuroblastoma resulted in a COG phase 2 trial in this disease also led by Dr. Fox. This study has enrolled patients ahead of schedule and is close to completion. The Section has also opened a novel phase 1/2 trial of vandetanib in children with MEN and medullary thyroid carcinoma. This is the first trial to include an extramural investigator (Dr. Sam Wells) as an adjuvant PI, and it has accrued patients from around the world, primarily with MEN 2B. Overall, vandetanib has been well tolerated and most patients enrolled on this trial have experienced tumor shrinkage during treatment with vandetanib. The Section has a collaborative initiative to manufacture a drug development tissue microarray to aid in selecting the new molecularly targeted drugs that are best suited for development in childhood cancers.

药理学与实验治疗 (PET) 部门专注于新抗癌药物的选择和临床开发，用于治疗儿童癌症、神经纤维瘤病（由 Brigitte Widemann 博士领导）和患有遗传性癌症易感综合征的儿童发生的癌症（Dr. Brigitte Widemann 领导）。维德曼）。该科有一个积极的临床试验计划来研究这些药物在儿童中的毒性、活性、药代动力学和药效学。临床试验作为单一机构研究或与其他儿童癌症中心或合作团体合作进行。研究了多种药物，包括分子靶向药物（如凡德他尼和 R1507）、细胞毒性药物（如曲贝替定）、抗血管生成药物（如西地尼布）、单克隆抗体以及调节抗癌药物治疗或毒性作用的药物（如奥拉帕尼、他拉博司他和塔利奎达） 。该科与癌症治疗评估计划和制药行业合作，确保在儿童中研究有前景的新药。该科是 COG 第一阶段/试点联盟和 COG 的非资助成员。这使得该科第一期试验中研究的药物（例如 ABT-751、伊沙匹隆）转移到合作组的第二期试验中。例如，由Elizabeth Fox博士领导的ABT-751 I期试验评估了两种给药方案，共入组了76名患者，其中包括50名神经母细胞瘤患者。初步数据表明该药物对神经母细胞瘤具有临床活性，导致 Fox 博士领导了一项针对这种疾病的 COG 2 期试验。这项研究已提前招募患者，并已接近完成。该科还针对患有 MEN 和甲状腺髓样癌的儿童开展了一项新的 vandetanib 1/2 期试验。这是第一个纳入外部研究者（Sam Wells 博士）作为辅助 PI 的试验，它已经招募了来自世界各地的患者，主要是 MEN 2B。总体而言，凡德他尼的耐受性良好，参加本试验的大多数患者在凡德他尼治疗期间都经历了肿瘤缩小。该科开展了一项合作计划，生产药物开发组织微阵列，以帮助选择最适合儿童癌症开发的新分子靶向药物。