Patient-derived-organoid (PDO) Guided Versus Conventional Therapy for Advanced Inoperable Abdominal Tumors

Phase 2

Withdrawn

• Conditions: Organoids
• Interventions: Drug: PDO-guided treatment; Drug: standard of care

• Registration Number: NCT05378048
• Lead Sponsor: Chinese University of Hong Kong

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2022-05-12
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-17
• Study Start: 2022-07-04
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-27
• Last Update Posted: 2023-03-29
• Primary Completion: 2025-07-03
• Study Completion: 2025-07-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• 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 11. [ 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.

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Exclusion Criteria

• unable to give consent, could not obtain a biopsy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PDO-guided treatment	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.
standard of care	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.

Primary Outcome Measures

Name	Time	Method
Tumor progression-free survival	12 months after randomization	The length of time after patients have received treatment and have no detectable disease and have no detectable disease

Secondary Outcome Measures

Name	Time	Method
tumour response rates	12 months after randomization	the assessment of the tumor burden (TB) after the treatment
rate of successful organoid culture and drug screen organoid culture	4-6 weeks after culture	the percentage of survival organoid and the availability of at least one drug to which PDO responds
the rate of overall survival	12 months after randomization	the percentage of people who are alive
rate of serious adverse events	12 months after randomization	the rate of side effects of drug, prolonging the hospitalization

Trial Locations

Locations (1)

Department of surgery , Prince of Wales Hospital; 🇭🇰 Hong Kong, N.t., Hong Kong