The PLATON Network

Study Overview
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Brief Summary
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The PLATON Network study is designed to elevate personalized therapy based on genomic tumor profiles in gastrointestinal cancer patients. Hereby, PLATON's study-design focuses on the patient's tumor molecular profiling. Within the network a web application will be developed to link clinical investigators and information on study sites, cancer patients and genetic alteration data, as well as available clinical trials at PLATON's study sites.

Detailed Description
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The PLATON Network is established as permanent open, multicenter, prospective, cohort study of patients with gastrointestinal cancer. The study design includes a study-specific biobank and a shared platform infrastructure for associated sub-studies and analysis projects. Within PLATON results of genetic tests of different research projects like the PLATON pilot-study (NCT04484636) as well as Next-generation deep sequencing (NGS) according to local protocols will be documented - compiling genomic tumor-profiles including tumor mutational burden (TMB) and microsatellite instability (MSI). The PLATON Network infrastructure is designed to increase the likelihood of treating the patients with an individualized therapy in available clinical studies. Therefore, molecular profiling must go hand in hand with inter-linking physicians and increasing inter-centre transparency. The feasibility of this approach will be tested in the PLATON Network, keeping in mind the vision of cancer patients receiving the best available, scientifically founded, biomarker-based care, tailored to his or her individual needs.

Official Title
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The Platform for Analyzing Targetable Tumor Mutations Network (Main-study)

Conditions
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Hepatocellular Cancer, Oesophageal Cancer, Cholangiocarcinoma, Gallbladder Cancer, Pancreatic Cancer, Stomach Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of hepatocellular carcinoma or intra- cholangiocarcinoma, extrahepatic cholangiocarcinoma or gallbladder carcinoma or pancreatic ductal adenocarcinoma or esophagogastric adenocarcinoma in the advanced setting (adjuvant or neoadjuvant therapy is allowed if completed 6 months prior to enrolment) and no local curative therapy available Standard first line therapy is planned, or patient is currently receiving first-line therapy Available tumor-genomic profile ( ≥50-gene panel assay; approved and assessed by central review), unless central tumor genomic profiling is done within a sub-study ECOG 0-2 Life expectancy ≥ 6 months Exclusion Criteria: Not able to understand all implications of study participation No written informed consent Age < 18 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HCC (Hepatocellular cancer)<br>Hepatocellular cancer patients with NGS based molecular tumor profiling | |
| CCA/GBCA (Intra-, extrahepatic cholangiocellular carcinoma or gallbladder cancer)<br>Intra-, extrahepatic cholangiocellular carcinoma or gallbladder cancer patients with NGS based molecular tumor profiling | |
| PanCa (Pancreatic cancer)<br>Pancreatic cancer patients with NGS based molecular tumor profiling | |
| EC/GC (Oesophagogastric cancer)<br>Oesophagogastric cancer patients with NGS based molecular tumor profiling | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of targetable mutations in gastrointestinal cancer patients | Relative frequency of targetable mutations computed as the number of patients who harbor at least one mutation divided by the number of total patients in the analyzed patient population | annual interim-analysis (1 year) | 
| Tumor mutations and their impact on treatment decisions in gastrointestinal cancer patients | Number of received therapies in or out accordance to genomic profiles | annual interim-analysis (1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) in genetically defined cohorts in gastrointestinal cancer patients | Overall survival measurement over time grouped by diagnostic cohorts and adjusted by age and sex will be correlated to treatments, while genomic profiles had or had not impact on decision for treatment. | annual interim-analysis (1 year) | 
| QoL via EQ-5D-5L questionnaire in genetically defined cohorts in gastrointestinal cancer patients | QoL measurements are done over time in the palliative setting. Gastrointestinal cancer patient cohorts will be grouped by diagnostics and adjusted by age and sex, correlated to treatments, while genomic profiles had or had not impact on decision for treatment in gastrointestinal cancer patients. EQ-5D data is used in summary statistics at each observational timepoint and to estimate the difference between health states like Mobility, Looking After Myself, Doing Usual Activities, Having Pain or Discomfort, Feeling Worried, Sad or Unhappy in diagnostic groups of different treatments over time. The EQ VAS (visual analogue scale) on a scale from 0 (the worst imaginable health) to 100 (the best imaginable health) indicates patients´ overall health on the day of questionnaire completion and will be used as measure of central tendency and dispersion | annual interim-analysis (1 year) | 
| QoL via EORTC QLQ-C30 questionnaire in genetically defined cohorts in gastrointestinal cancer patients | QoL measurements are done over time in the palliative setting. Gastrointestinal cancer patient cohorts will be grouped by diagnostics and adjusted by age and sex, correlated to treatments, while genomic profiles had or had not impact on decision for treatment in gastrointestinal cancer patients. EORTC QLQ-C30 data is used in summary statistics at each observational timepoint to analyze five function subscales (physical, role, emotional, cognitive and social), nine symptom subscales/items (fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties) and a global health/ QoL subscale following the QLQ-C30 scoring manual. | annual interim-analysis (1 year) | 
| QoL via EORTC QLQ-BIL21 questionnaire in genetically defined cohorts of CCA and GBCA patients | QoL measurements are done over time in the palliative setting. The CCA and GBCA patients cohort will be adjusted by age and sex, correlated to treatments, while genomic profiles had or had not impact on decision for treatment. QoL in CCA and GBCA patients will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) Questionnaire QLQ-BIL21 and analyzed according validated manual, forming nine symptom subscales/items for Eating, Jaundice, Tiredness, Pain and Anxiety. | annual interim-analysis (1 year) | 
| QoL via EORTC QLQ-HCC18 questionnaire in genetically defined cohorts of HCC patients | QoL measurements are done over time in the palliative setting. The HCC patient cohort will be adjusted by age and sex, correlated to treatments, while genomic profiles had or had not impact on decision for treatment. QoL in HCC patients will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) Questionnaire QLQ-HCC18 and analyzed according validated manual, forming symptom scales for Fatigue, Body Image, Jaundice, Nutrition, Pain and Fever as well as single items like Abdominal swelling and Sex life in summary statistics at each observational timepoint. | annual interim-analysis (1 year) | 
| QoL via EORTC QLQ-PAN26 questionnaire in genetically defined cohorts of PDCA patients | QoL measurements are done over time in the palliative setting. The PDCA patient cohort will be adjusted by age and sex, correlated to treatments, while genomic profiles had or had not impact on decision for treatment. QoL in PDCA patients will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) Questionnaire QLQ-PAN26 and analyzed according validated manual, forming eight scales to assess Pancreatic pain, Digestive symptoms, Altered bowel habit, Hepatic, body image, Satisfaction with health care, and Sex life in summary statistics at each observational timepoint. | annual interim-analysis (1 year) | 
| QoL via EORTC QLQ-STO22 questionnaire in genetically defined cohorts of EC/GC patients | QoL measurements are done over time in the palliative setting. The EC/GC patient cohort will be adjusted by age and sex, correlated to treatments, while genomic profiles had or had not impact on decision for treatment. QoL in EC/GC patients will be measured using the European Organisation for Research and Treatment of Cancer (EORTC) Questionnaire QLQ-STO22 and analyzed according validated manual, forming five multi-item scales to assess dysphagia, pain, reflux, eating and anxiety as well as four single items like dry mouth, taste, body image and hair loss in summary statistics at each observational timepoint. | annual interim-analysis (1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric cancer, Individualized cancer therapy, Targetable mutations, NGS, Hepatocellular Cancer, Cholangiocarcinoma, Gallbladder Cancer, Pancreatic Cancer, Oesophageal Cancer, Stomach Cancer, Platform-Design, Biobanking