Abstract

Background

One third of patients with (R/M SCCHN) are not eligible to receive the standard first-line chemotherapy EXTREME (cisplatin, fluorouracile and cetuximab). In this population, the weekly scheme of carboplatin-paclitaxel demonstrated clinical efficacy an overall survival (OS) of 4.9-12.8 months and a response rate of 20-52%. In a study conducted in our center, patients ineligible to EXTREME due to performance status (PS) 2 or other reasons (excluding PS2) reached a median OS of 3.6 months and 11.5 months, respectively.

Trial Design

A prospective, multicenter, single-arm phase II trial to study the efficacy and safety of durvalumab (anti-PD-L1) combined with carboplatin-paclitaxel in patients with R/M SCCHN ineligible to cisplatin. A first cohort of patients (n = 64) with PS0-1 will be accrued, then a cohort of patients with PS2 (n = 38) if results of the cohort PS0-1 are positive. Patients will receive four 28-day cycles (carboplatin AUC2 and paclitaxel 80mg/m², D1, D8, D15) with 4-weekly infusions of 1500mg durvalumab (pursued for a maximum of 12 months). An initial safety run-in step with predefined stopping rules is being conducted in the first 6 patients of the cohort PS0-1. The primary objective will be to determine the efficacy (12-month OS rate) of the combination. The treatment will be considered for further investigations, if at least 38 successes and 10 successes are observed in cohorts PS0-1 and PS2, respectively. Secondary endpoints will also be investigated: progression-free survival, time-to-treatment failure, OS, response rates, quality of life (QLQ-C30 and QLQ-H&N35) and tolerance profile of the combination. Radiological endpoints will be evaluated using the RECIST version 1.1. Translational objectives will be to study blood and tumor markers (expression of immune checkpoints, immune infiltrate and molecular alterations) as predictive and prognostic factors of efficacy. As of Oct 2^nd 2019, a total of 5 patients has been accrued in the safety run-in step.

Clinical trial identification

NCT0372967.

Legal entity responsible for the study

Centre Léon Berard.

Funding

AstraZeneca.

Disclosure

J. Fayette: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Innate Pharma; Honoraria (self): Merck; Honoraria (self): Rakuten; Honoraria (self): Biogen.

中文翻译：

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90TiP FRAIL-IMMUNE：多发性，前瞻性，单臂II期将durvalumab与卡铂和紫杉醇联合作为头颈部复发/转移性鳞状细胞癌患者的一线治疗（GORTEC 2018 -03）

抽象的

背景

三分之一（R / M SCCHN）患者没有资格接受标准的一线化疗EXTREME（顺铂，氟尿嘧啶和西妥昔单抗）。在该人群中，卡铂-紫杉醇的每周方案显示出临床疗效，总生存期（OS）为4.9-12.8个月，缓解率为20-52％。在我们中心进行的一项研究中，由于表现状态（PS）2或其他原因（不包括PS2）而不符合EXTREME的患者的OS中位数分别为3.6个月和11.5个月。

试验设计

一项前瞻性，多中心，单臂II期临床试验，用于研究durvalumab（抗PD-L1）联合卡铂-紫杉醇在不适用顺铂的R / M SCCHN患者中的疗效和安全性。如果PS0-1队列的结果为阳性，则将收集第一批PS0-1的患者队列（n = 64），然后再收集PS2的患者队列（n = 38）。患者将接受四个28天的周期（卡铂AUC2和紫杉醇80mg /m²，D1，D8，D15），并每周4次输注1500mg durvalumab（最长12个月）。在队列PS0-1的前6名患者中，进行了具有预定义的停止规则的初始安全磨合步骤。主要目标是确定联合用药的疗效（12个月OS率）。该治疗方法将被考虑作进一步调查，如果在队列PS0-1和PS2中分别观察到至少38次成功和10次成功。次要终点也将进行调查：无进展生存期，治疗失败时间，OS，缓解率，生活质量（QLQ-C30和QLQ-H＆N35）和组合的耐受性。放射学终点将使用RECIST 1.1版进行评估。转化目标将是研究血液和肿瘤标志物（免疫检查点的表达，免疫浸润和分子改变）作为疗效的预测和预后因素。截至10月2日 放射学终点将使用RECIST 1.1版进行评估。转化目标将是研究血液和肿瘤标志物（免疫检查点的表达，免疫浸润和分子改变）作为疗效的预测和预后因素。截至10月2日 放射学终点将使用RECIST 1.1版进行评估。转化目标将是研究血液和肿瘤标志物（免疫检查点的表达，免疫浸润和分子改变）作为疗效的预测和预后因素。截至10月2日^到2019年，安全磨合步骤共计招募了5名患者。

临床试验鉴定

NCT0372967。

负责研究的法人实体

中心莱昂·贝拉德。

资金

阿斯利康。

揭露

J. Fayette：Honoraria（个体）：Bristol-Myers Squibb；酬金（个体经营），研究资助/资助（个体经营）：阿斯利康；Honoraria（个体）：MSD; Honoraria（个体）：先天制药; Honoraria（个体）：默克; Honoraria（个体）：乐天; Honoraria（个体）：Biogen。