Patient-derived-organoid (PDO) Guided Versus Conventional Therapy for Advanced Inoperable Abdominal Tumors: a Multicenter Open-label, Proof of Concept, Phase 2 Randomised Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Tumor progression-free survival
研究概览
简要总结
Recent studies that ex vivo drug responses on PDO models across different solid tumours can predict treatment responses to chemotherapeutic agents. In patients with metastatic or inoperable solid abdominal tumours, we perform a PDO based drug screen and to identify drugs that will confer clinical response and compared to conventional treatments
详细描述
Precision oncology aims to improve the clinical outcomes of patients by offering personalized treatment through identifying druggable genomic aberrations within their tumours. However, current challenges in cancer treatment have hampered the broad clinical utility of the gene-drug associations in the clinic. This is particularly valid when it comes to offering alternative treatment options for advanced inoperable patients with chemo-refractory diseases. There is currently no reliable biomarker to predict treatment response. Patient-derived organoids (PDOs) closely resemble both pheno- and genotypically to patients' tumours. In observational studies, anticancer drug screening ex vivo on PDOs has been shown to predict clinical response with high sensitivity and specificity. PDO-based drug screen represents a truly personalised platform by predicting patient-specific drug response with high accuracy. Recent technical advancements in growing these PDO 'avatars' from biopsies have made it possible to find anticancer drug options in tumours from advanced inoperable patients, and explore new possibilities for treatment options that otherwise would be missed by standard conventional therapies. PDO-based drug assays permit examination of combinatorial drug testing ex vivo and potentially offer patients treatment options. The clinical utility of treatment based on PDO informed drug options however has not been established. We hypothesize that treatment guided by PDO-based drug screens, when compared to conventional treatment, can lead to better treatment response and clinical outcomes. We propose a phase 2 proof-of-concept randomized controlled trial in patients with inoperable or metastatic abdominal tumours refractory to at least one chemotherapeutic agent. Our primary endpoint to this randomised trial is progression-free survival (PFS) at 12 months. In this trial, we in addition expand our current bio-resource of PDOs, and further valid PDO guided treatment model by comparing ex vivo PDO drug response to patients' clinical response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients should be older than 18 years, able to provide written consents to trial participation, with Eastern cooperative oncology group performance status of 0 or 1, With measurable disease in accordance with response evaluation criteria in solid tumours (RECIST) version
- •[ 10 ] With a neutrophil count, hemoglobin > 9g/dl, serum creatinine <1.5 x upper limit of normal, serum bilirubin < 1.5 x normal, and aspartate and alanine aminotransferases (<3 x ULN or <5x in those with liver metastasis) Ejection Fraction >50% of normal. The disease is accessible for a biopsy (radiologic or endoscopic) or resection of a metastatic site.
排除标准
- •unable to give consent, could not obtain a biopsy
研究组 & 干预措施
PDO-guided treatment
A biopsy of the tumour will be performed for PDO culture and Genome-guided drug screening.
An Multidisciplanary Tumour Board will review the drug screen results and recommend the use of a drug with a response in a PDO.
干预措施: PDO-guided treatment (Drug)
standard of care
the standard of care will include all treatments that have been reported to improve survival or quality of life in randomized trials.
干预措施: standard of care (Drug)
结局指标
主要结局
Tumor progression-free survival
时间窗: 12 months after randomization
The length of time after patients have received treatment and have no detectable disease and have no detectable disease
次要结局
- tumour response rates(12 months after randomization)
- rate of successful organoid culture and drug screen organoid culture(4-6 weeks after culture)
- the rate of overall survival(12 months after randomization)
- rate of serious adverse events(12 months after randomization)
研究者
James Yun-wong Lau
professor
Chinese University of Hong Kong