研究方案：一项多中心、随机对照临床试验，探索局部晚期胰腺癌的基质靶向治疗；STARPAC2。

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

作者信息

Kocher Hemant M, Sasieni Peter, Corrie Pippa, McNamara Mairéad G, Sarker Debashis, Froeling Fieke E M, Christie Alan, Gillmore Roopinder, Khan Khurum, Propper David

机构信息

Barts Cancer Institute and Wolfson Institute of Public Health, Mary University of London, John Vane Science Centre, Charterhouse Square, London, Queen, EC1M 6BQ, UK.

Barts Health NHS Trust, Whitechapel, London, E1 1BB, UK.

出版信息

BMC Cancer. 2025 Jan 20;25(1):106. doi: 10.1186/s12885-024-13333-z.

DOI:10.1186/s12885-024-13333-z

PMID:39833722

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11748870/

Abstract

BACKGROUND

Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

METHODS

Patients with laPDAC will receive at least six cycles of GEM-NABP with 1:1 randomisation to receive this with or without ATRA to assess response, until progression or intolerance. Those with stable/responding disease may undergo surgical resection. Primary endpoint is progression free survival (PFS) defined as the time from the date of randomisation to the date of first documented tumour progression (response evaluation criteria in solid tumours [RECIST] v1.1) or death from any cause, whichever occurs first. Secondary endpoints include objective response rate (ORR), overall survival (OS), safety and tolerability, surgical resection rate, R0 surgical resection rate and patient reported outcome measures (PROMS) as measured by questionnaire EQ-5D-5L. Exploratory endpoints include a decrease or increase in CA19-9 and serum Vitamin A over time correlated with ORR, PFS, and OS.

DISCUSSION

STARPAC2 aims to assess the role of stromal targeting in laPDAC.

TRIAL REGISTRATION

EudraCT: 2019-004231-23; NCT04241276; ISRCTN11503604.

摘要

背景

胰腺癌（PDAC：胰腺导管腺癌，最常见的类型）是一种致命疾病，最佳治疗方法是手术切除，但只有不到五分之一的患者可行。约三分之一的患者表现为局部晚期、无法手术、无转移（laPDAC），其标准治疗是姑息化疗；少数患者可缩小至足以进行手术切除。我们提出一项II期临床试验，以测试标准化疗（吉西他滨与纳米白蛋白结合型紫杉醇：GEM-NABP）与重新利用全反式维甲酸（ATRA）靶向基质相结合是否可以延长laPDAC患者的无进展生存期，并使其成功进行手术切除，因为I B期临床试验的数据表明GEM-NABP-ATRA联合用药对晚期PDAC患者具有安全性且可能有治疗益处。

方法

laPDAC患者将接受至少六个周期的GEM-NABP治疗，并按1:1随机分组，分别接受联合或不联合ATRA的治疗，以评估疗效，直至疾病进展或出现不耐受。疾病稳定/有反应的患者可接受手术切除。主要终点是无进展生存期（PFS），定义为从随机分组日期到首次记录肿瘤进展（实体瘤疗效评价标准[RECIST]v1.1）或任何原因导致死亡的日期，以先发生者为准。次要终点包括客观缓解率（ORR）、总生存期（OS）、安全性和耐受性、手术切除率、R0手术切除率以及通过EQ-5D-5L问卷测量的患者报告结局指标（PROMS）。探索性终点包括CA19-9和血清维生素A随时间的降低或升高与ORR、PFS和OS的相关性。