Abstract：
BACKGROUND: An increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30-80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer treatment on clinical outcomes still needs investigation.
METHODS: ProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0-2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon\'s two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing.
CONCLUSIONS: The ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy.
METHODS: 16, 09-MAY-2022.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04341181. Secondary Identifying No: ML41742. EudraCT No: 2019-004771-40.
METHODS: ProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0-2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon\'s two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing.
CONCLUSIONS: The ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy.
METHODS: 16, 09-MAY-2022.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04341181. Secondary Identifying No: ML41742. EudraCT No: 2019-004771-40.
摘要：
背景：越来越多的试验表明，当靶向治疗与个体患者（pts）的药物基因组改变相匹配时，患有转移性疾病的癌症患者的治疗结果得到改善。估计30-80%的晚期实体瘤具有可操作的基因组改变。然而,个性化癌症治疗的疗效仍然很少在更大的研究，由于不同组织学肿瘤类型之间的可药物改变的低频率和异质性分布，因此进行了对照试验。因此,靶向癌症治疗对临床结局的总体影响仍需研究.
方法：ProTarget是一个国家，非随机化，多种药物，开放标签，泛癌症2期试验旨在研究目前市售13种的抗肿瘤活性和毒性，EMA批准的靶向治疗晚期恶性疾病的标记适应症之外，具有特定的可操作的基因组改变。该试验涉及丹麦国家分子肿瘤委员会，以确认药物变体匹配。主要纳入标准包括a)可测量的疾病(RECISTv.1.1)，b)ECOG性能状态0-2,和c)与研究药物之一匹配的可操作的基因组改变。关键排除标准包括a）所选药物的EMA批准标签中的癌症类型，和b)已知赋予药物抗性的基因组改变。初始药物剂量，时间表和剂量修改是根据EMA批准的标签。主要终点是16周时的客观反应或疾病稳定。将Pts分配给所选药物定义的队列，基因组改变，和肿瘤组织学类型。队列根据Simon的两阶段设计进行监控。前24周每8周评估一次反应，然后每12周。该试验的设计类似于荷兰DRUP和ASCOTAPUR试验，是北欧精准癌症医学试验网络的合作伙伴。在ProTarget中,连续新鲜肿瘤和液体活检是强制性的，并收集用于广泛的翻译研究，包括全基因组测序，阵列分析，和RNA测序。
结论：ProTarget试验将为靶向治疗确定新的预测性生物标志物，并提供新的数据和有关分子途径的必要见解，例如，耐药机制，从而有可能发展和扩大个性化癌症治疗策略。
方法：2022年9月16日。
背景：ClinicalTrials.gov标识符：NCT04341181。二级识别号：ML41742。欧盟编号：2019-004771-40。
方法：ProTarget是一个国家，
结论：ProTarget试验将为靶向治疗确定新的预测性生物标志物，并提供新的数据和有关分子途径的必要见解，例如，
方法：2022年9月16日。
背景：ClinicalTrials.gov标识符：NCT04341181。
