PDF(Pubmed)
Abstract：
BACKGROUND: PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer.
METHODS: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101.
CONCLUSIONS: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04678102 .
METHODS: Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101.
CONCLUSIONS: PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04678102 .
摘要：
背景：PHI-101是一种口服可用的，选择性检查点激酶2（Chk2）抑制剂。在临床前实验中，PHI-101在卵巢癌细胞系和受损的DNA修复途径中显示出抗肿瘤活性。此外，体内研究提示PHI-101与PARP抑制剂联合治疗卵巢癌具有协同作用.这项研究的主要目的是评估PHI-101在铂耐药的复发性卵巢癌中的安全性和耐受性。
方法：Chk2抑制剂治疗复发性上皮组织，FallopIan,或OVarian癌症(CREATIVE)试验是一项前瞻性试验，多中心,IA期剂量递增研究。计划六个剂量水平队列，预计将有6~36名患者参加本试验.主要纳入标准包括组织学确诊的上皮性卵巢癌≥19岁，输卵管癌,或原发性腹膜癌。此外，包括在铂类化疗期间显示疾病进展或在完成铂类化疗后24周内出现疾病进展的患者,和超过5个的先前化疗路线将被排除。这项研究的主要终点是确定PHI-101的剂量限制性毒性（DLT）和最大耐受剂量（MTD）。
结论：PHI-101是第一种口服可用的Chk2抑制剂，有望显示出治疗复发性卵巢癌的有效性。通过这个创造性的审判,这种新的靶向治疗的DLT和MTD可以被证实为II期临床试验找到推荐剂量。这项研究可能有助于开发一种治疗卵巢癌的新组合方案。
背景：ClinicalTrials.gov标识符：NCT04678102。
方法：Chk2抑制剂治疗复发性上皮组织，
结论：PHI-101是第一种口服可用的Chk2抑制剂，
背景：ClinicalTrials.gov标识符：NCT04678102。
