Tests tumor-derived organoids to guide treatment in advanced liver and bowel cancers

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with advanced, inoperable or spread solid tumors who did not respond to at least one standard drug treatment. Treatment is guided by gene tests and lab-grown copies of the tumor.

Age

Over 18 years old (the record lists 18 to 100 years).

Sex

All sexes can join.

Disease stage

Metastatic, inoperable or advanced solid tumors that did not respond to at least one standard chemotherapy or targeted drug. The disease must be measurable (RECIST 1.1) and reachable for a biopsy or surgery of a metastatic site.

Earlier treatment

Must have had at least one standard chemotherapy or targeted drug that did not work. People are first seen at a multidisciplinary tumor board meeting.

Main reasons for not taking part

• Cannot give informed consent
• Not fit for standard chemotherapy, for example low neutrophil count, hemoglobin 9 g/dl or lower, or ejection fraction 50% or lower on echocardiography
• Performance status (daily activity level) above 1
• Tumor cannot be reached for a biopsy or resection

The registry criteria, word for word

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

• Are you between 18 and 100 years old?YesNo

What the trial wants to find out

Precision oncology aims to improve clinical outcome of patients by offering personalized treatment through identifying druggable genomic aberrations within their tumors. This is particularly valid when it comes to offering alternative treatment options for patients with advanced tumors that are chemo-refractory. Patient-derived organoids (PDOs) are 3 dimensional tumoroids that can be expanded ex vivo and are both pheno- and genotypically identical to patients' tumors. Observational studies have shown that PDO-based drug screens can predict treatment response with high sensitivity and specificity. Vlachogiannis G. reported a living biobank of patient-derived organoids (PDOs) from patients with advanced GI cancers enrolled in clinical trials. PDOs can recapitulate patients' clinical response to chemotherapeutic agents. In 19 tumor organoids, the group performed molecular profiling and drug screens and then compared ex vivo organoid responses to anticancer drugs. Drug response to PDO based orthotopic mouse tumor xenografts correlated to the drug response of the patient in clinical trials. Further to the study, there were other retrospective validation studies utilizing PDOs from patients enrolled in clinical trials such as the TUMOROID, CinClare to predict clinical response. Ooft studied PDOs from patients with metastatic colorectal cancers enrolled in the TUMOROID study to predict response to irinotecan-based therapies. Yao generated a organoid biobank of 80 locally advanced rectal cancers. These patients were derived from a phase III study (CinClare) that compared neoadjuvant chemo-radiation using either capecitabine or CAPIRI. Response to chemoradiation in patients matched to that of rectal cancer organoids (sensitivity 78% and specificity 91.9%). In a systematic analysis of 17 studies (9 on advanced GI and pancreatic cancers, one on renal cell cancer and others on miscellaneous cancers), the pooled sensitivity and specificity for discriminating patients with a clinical response through PDO-based drug screen was 0.81 (95%CI 0.69-0.89) and 0.74 (95%CI 0.64-0.82) respectively. Within 4-6 weeks, PDO-based drug screen creates a true 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 test suitable anticancer drugs in patients with advanced inoperable tumors, and explore the new possibilities for treatment options that otherwise would be missed by standard conventional therapies. In 2019, our group embarked on PDO research; investigators obtained tissues from patients with advanced/ inoperable solid tumors, and performing drug screens on these PDOs ex vivo. In several patients, investigators were able to identified drugs not otherwise used through sequencing data, and observed remarkable clinical response in patients with PDO responsive tumors. Investigators illustrate with cases that underwent PDO culture and drug screens. [ See appendix ] In the literature, the clinical utility of treatment based on PDO informed drug options has however not been fully established. Investigators therefore propose a phase 2 proof-of-concept clinical trial to evaluate efficacy of NGS/ PDO guided treatment in patients with inoperable or metastatic solid tumors..

The group in the trial

• Patient-Derived Tumor Organoids (PDO) Guided TherapyTreatment being tested

  Intervention in this study is to perform tissue sampling to patient's tumor which are then subjected to DNA extraction for whole exome sequencing, organoid culture, and drug screen. An MDT board will review the drug screen results and excluded drug choice of poor response. Then the referring oncologist has the final discretion on the choice of chemo- or targeted agent as usual.

  Treatment: Patient-Derived Tumor Organoids