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

NCT ID: NCT05378048

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-04
• Study Completion Date: 2025-07-03

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.

Conditions

Organoids

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

PDO-guided treatment

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

standard of care

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

James Yun-wong Lau

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of surgery , Prince of Wales Hospital

Hong Kong, N.T., Hong Kong

Countries

Hong Kong

Other Identifiers

PDO

Identifier Type: -

Identifier Source: org_study_id