Clinical trial NCT05378048: Patient-derived-organoid (PDO) Guided Versus Conventional Therapy for Advanced Inoperable Abdominal Tumors
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Organoids
Keywords: Organoids
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-05-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patients are randomized to PDO-guided treatment or standard of care.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Tumor progression-free survival
timeFrame: 12 months after randomization
Secondary outcomes:
measure: the rate of overall survival
timeFrame: 12 months after randomization
measure: tumour response rates
timeFrame: 12 months after randomization
measure: rate of successful organoid culture and drug screen organoid culture
timeFrame: 4-6 weeks after culture
measure: rate of serious adverse events
timeFrame: 12 months after randomization
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of surgery , Prince of Wales Hospital
state: N.t.
Study officials:
References: