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首页> 美国卫生研究院文献>Neuro-Oncology >DIPG-76. PNOC-003: PRECISION MEDICINE TRIAL FOR CHILDREN WITH DIFFUSES INTRINSIC PONTINE GLIOMA: PRELIMINARY EXPERIENCE WITH MULTI-AGENT PERSONALIZED THERAPY RECOMMENDATIONS
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DIPG-76. PNOC-003: PRECISION MEDICINE TRIAL FOR CHILDREN WITH DIFFUSES INTRINSIC PONTINE GLIOMA: PRELIMINARY EXPERIENCE WITH MULTI-AGENT PERSONALIZED THERAPY RECOMMENDATIONS

机译：DIPG-76。 PNOC-003：患有弥漫性内在性胶质神经胶质瘤的儿童的精密药物试验：结合多代理商个性化治疗建议的初步经验

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New therapies for children with diffuse intrinsic pontine glioma (DIPG) are greatly needed. Within a prospective multi-center feasibility trial, we evaluated whether genomic profiling (tumor and germline exome sequencing and tumor RNA) could be used to identify targetable events to inform a treatment recommendation from a multidisciplinary tumor board within 21 business days after biopsy recommending up to four FDA approved drugs to start following focal radiotherapy. Agents were prioritized that target DNA alterations and have available pediatric safety and dosing information. Agents were introduced in a sequential manner with close toxicity monitoring when there was limited experience for the combinations. Seventeen patients were enrolled. Fourteen of the 15 eligible patients had complete profiling and generation of a tumor board recommendation. Eight patients followed the treatment recommendation. Panobinostat was used as the backbone of therapy for the majority of patients with histone mutations with a starting dose of 16mg/m2/dose three times a week for 2 weeks followed by a 1-week break with dose escalation as tolerated. Administered doses of panobinostat ranged from 15-37mg/m2/dose with most patients tolerating a 15-24mg/m2 dose for 2–12 cycles of therapy. Several patients remain on study therapy. Additional agents recommended in combination included etoposide, cabozantinib, mebendazole, dabrafenib, trametinib, minocycline, carboplatin, metformin, dasatinib, and everolimus. Therapy has been generally well tolerated without unexpected severe toxicities. Reported grade 3 or greater treatment related toxicities include ALT elevation, mucositis, hypertension, hypertriglyceridemia, and hypokalemia and hematologic toxicities. The study has been expanded to evaluate preliminary efficacy of this approach.
机译：急需用于弥散性桥脑神经胶质瘤（DIPG）患儿的新疗法。在一项前瞻性的多中心可行性试验中，我们评估了是否可以使用基因组图谱（肿瘤和生殖系外显子组测序以及肿瘤RNA）来确定可靶向事件，从而在活检推荐后的21个工作日内从多学科肿瘤委员会提供治疗建议。四种FDA批准的药物可在局部放疗后开始使用。优先考虑了靶向DNA改变并具有可用的儿科安全性和剂量信息的药物。当组合的经验有限时，以连续的方式引入药物，并密切监测毒性。十七名患者入组。 15名符合条件的患者中有14名具有完整的概况分析并生成了肿瘤委员会的推荐意见。 8名患者遵循了治疗建议。对于大多数具有组蛋白突变的患者，将Panobinostat用作治疗的骨干，每周3次开始剂量16mg / m2 /剂量，持续2周，然后中断1周，并允许耐受剂量的递增。 Panobinostat的给药剂量范围为15-37mg / m2 /剂量，大多数患者在2-12个疗程中耐受15-24mg / m2的剂量。几名患者仍在接受研究治疗。推荐组合使用的其他药物包括依托泊苷，卡博替尼，甲苯达唑，达布拉非尼，曲美替尼，米诺环素，卡铂，二甲双胍，达沙替尼和依维莫司。一般而言，治疗耐受性良好，没有意外的严重毒性。报道的3级或更高级别的治疗相关毒性包括ALT升高，粘膜炎，高血压，高甘油三酯血症，低钾血症和血液学毒性。这项研究已经扩大到评估这种方法的初步疗效。

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