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

Organoids Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05378048
• Other study ID #: PDO
• Status: Withdrawn
• Phase: Phase 2
• Start date: July 4, 2022
• Est. completion date: July 3, 2025

Study information

• Verified date: March 2023
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 3, 2025
• Est. primary completion date: July 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

Exclusion Criteria:

• unable to give consent, could not obtain a biopsy

Related Conditions & MeSH terms

• Abdominal Neoplasms
• Organoids

Intervention

Drug:
• 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
the standard of care will include all treatments that have been reported to improve survival or quality of life in randomized trials.

Locations

Country	Name	City	State
Hong Kong	Department of surgery , Prince of Wales Hospital	Hong Kong	N.t.

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor progression-free survival	The length of time after patients have received treatment and have no detectable disease and have no detectable disease	12 months after randomization
Secondary	the rate of overall survival	the percentage of people who are alive	12 months after randomization
Secondary	tumour response rates	the assessment of the tumor burden (TB) after the treatment	12 months after randomization
Secondary	rate of successful organoid culture and drug screen organoid culture	the percentage of survival organoid and the availability of at least one drug to which PDO responds	4-6 weeks after culture
Secondary	rate of serious adverse events	the rate of side effects of drug, prolonging the hospitalization	12 months after randomization