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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Organoids
• Intervention / Treatment: Drug: PDO-guided treatment; Drug: standard of care

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • N.t.
    • Hong Kong, N.t., Hong Kong
      • Department of surgery , Prince of Wales Hospital
      • Contact: James YW LAU, MD; Phone Number: +852350522640; Email: laujyw@surgery.cuhk.edu.hk
      • Contact: Karina Yu, MD; Phone Number: +85235052640; Email: karinayu@surgery.cuhk.edu.hk
      • Sub-Investigator: Stephen Lam chan, MD
      • Principal Investigator: James Lau, MD
      • Sub-Investigator: Nathalie wong, Ph D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of overall survival	the percentage of people who are alive	12 months after randomization
tumour response rates	the assessment of the tumor burden (TB) after the treatment	12 months after randomization
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
rate of serious adverse events	the rate of side effects of drug, prolonging the hospitalization	12 months after randomization

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Anticipated): July 4, 2022
• Primary Completion (Anticipated): July 3, 2025
• Study Completion (Anticipated): July 3, 2025

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Organoids
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Abdominal Neoplasms
• Other Study ID Numbers: PDO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No