PLATON - Platform for Analyzing Targetable Tumor Mutations (Pilot-study)

Study Overview
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Brief Summary
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PLATON (Platform for Analyzing Targetable Mutations) is a prospective, multicentre, observational cohort study with biobanking. In a first approach PLATON's pilot-study assesses genomic profiling in gastrointestinal cancer therapy and the frequencies of targetable mutations including Tumor Mutational Burden (TMB) and Microsatellite Instability Status (MSI), performing Next-generation deep sequencing (NGS) using the Foundation Medicine assays on tumor specimen and EDTA-whole blood samples. The Study Protocol does not define any further medical intervention or evaluate the efficacy or safety of the treatment decision made by the investigator. Another important objective of PLATON's pilot project is to evaluate whether and how many patients are treated based on their genomic profiles.

Detailed Description
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PLATON (Platform for Analyzing Targetable Mutations) is designed to improve personalized therapy for patients in different cancer entities, such as in hepatocellular cancer (HCC), intra- and extrahepatic cholangiocellular carcinoma (CCA), gallbladder carcinoma (GBCA), pancreatic cancer (PanCa) and esophagogastric cancer (EC/GC), and elevate the treatment guidance within its framework. The key to understand the mechanisms in initiation, progression and response to treatment of cancer is the data integration of genetic mutational signatures with medical and physiological data of diseased cohorts. PLATON is a prospective, multicentre, observational cohort study with biobanking and does not define any medical intervention or evaluate the efficacy or safety of the treatment decision made by the investigator.In a first approach PLATON's pilot-study assess genomic profiling in gastrointestinal cancer therapy and the frequencies of targetable mutations including Tumor Mutational Burden (TMB) and Microsatellite Instability Status (MSI), performing Next-generation deep sequencing (NGS) using the Foundation Medicine assays on tumor specimen and EDTA-whole blood samples. Another important objective of PLATON's pilot project is to evaluate whether and how many patients are treated based on their genomic profiles. The pilot-study starts with the national-wide enrolment of 200 participants of both sexes and ages over 18 at 40 german study sites. The long-term vision is to enable cancer patients to receive the best available, scientifically founded, biomarker-based care, tailored to his or her individual needs

Official Title
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PLATON - Platform for Analyzing Targetable Tumor Mutations (Pilot-study) A Multicenter, Prospective, Cohort Study To Assess The Genomic Profiles And Associated Therapy Decision In Gastrointestinal Cancer

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

Intervention / Treatment
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* Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of hepatocellular carcinoma or intra-/extrahepatic cholangiocarcinoma or gallbladder carcinoma or pancreatic ductal adenocarcinoma or esophagogastric adenocarcinoma in the advanced setting and no local curative therapy available. Standard first line therapy is planned, or patient is currently receiving first line therapy (started within the last 2 months before enrolment) 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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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Experimental Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hepatocellular Cancer<br>molecular profiling - hepatocellular cancer (HCC) | Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid<br>* FoundationOne CDx is a FDA-approved broad companion diagnostic (CDx) that is clinically and analytically validated for solid tumors. The test is designed to provide physicians with clinically actionable information - both to consider appropriate therapies for patients and understand results with evidence of resistance - based on the individual genomic profile of each patient's cancer. Every test result includes microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions. FoundationOne®Liquid is a liquid biopsy test for solid tumors that analyzes circulating tumor DNA (ctDNA) in blood.<br>|
| Other: Cholangiocarcinoma<br>molecular profiling - intra- and extrahepatic cholangiocellular carcinoma (CCA) | Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid<br>* FoundationOne CDx is a FDA-approved broad companion diagnostic (CDx) that is clinically and analytically validated for solid tumors. The test is designed to provide physicians with clinically actionable information - both to consider appropriate therapies for patients and understand results with evidence of resistance - based on the individual genomic profile of each patient's cancer. Every test result includes microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions. FoundationOne®Liquid is a liquid biopsy test for solid tumors that analyzes circulating tumor DNA (ctDNA) in blood.<br>|
| Other: Gallbladder Cancer<br>molecular profiling - gallbladder carcinoma (GBCA) | Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid<br>* FoundationOne CDx is a FDA-approved broad companion diagnostic (CDx) that is clinically and analytically validated for solid tumors. The test is designed to provide physicians with clinically actionable information - both to consider appropriate therapies for patients and understand results with evidence of resistance - based on the individual genomic profile of each patient's cancer. Every test result includes microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions. FoundationOne®Liquid is a liquid biopsy test for solid tumors that analyzes circulating tumor DNA (ctDNA) in blood.<br>|
| Other: Pancreatic Cancer<br>molecular profiling - pancreatic cancer (PanCa) | Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid<br>* FoundationOne CDx is a FDA-approved broad companion diagnostic (CDx) that is clinically and analytically validated for solid tumors. The test is designed to provide physicians with clinically actionable information - both to consider appropriate therapies for patients and understand results with evidence of resistance - based on the individual genomic profile of each patient's cancer. Every test result includes microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions. FoundationOne®Liquid is a liquid biopsy test for solid tumors that analyzes circulating tumor DNA (ctDNA) in blood.<br>|
| Other: Oesophageal Cancer + Stomach Cancer<br>molecular profiling - esophagogastric cancer (EC/GC) | Diagnostic Test: FoundationOne®CDx and FoundationOne®Liquid<br>* FoundationOne CDx is a FDA-approved broad companion diagnostic (CDx) that is clinically and analytically validated for solid tumors. The test is designed to provide physicians with clinically actionable information - both to consider appropriate therapies for patients and understand results with evidence of resistance - based on the individual genomic profile of each patient's cancer. Every test result includes microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions. FoundationOne®Liquid is a liquid biopsy test for solid tumors that analyzes circulating tumor DNA (ctDNA) in blood.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of mutations in patients with HCC, intra- and extrahepatic CCA, GBCA, PDAC and gastric cancer | Relative frequency of targetable mutations (incl. TMB and MSI status) computed as the number of patients who harbors at least one mutation divided by the number of total patients in the pooled patient population. | up to 4 weeks after biospecimen provision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heterogeneity of targetable alterations in paraffin embedded specimen vs. cfDNA | Number of differences (heterogeneity) in targetable alterations in paraffin specimen vs. cfDNA | up to 4 weeks after biospecimen provision | 
| Relative frequency of targetable mutations (incl. TMB and MSI status) per disease group | Relative frequency of targetable mutations (incl. TMB and MSI status) per disease group | up to 4 weeks after biospecimen provision | 
| Number of patients receiving therapies in accordance to their genomic profiles | Number of patients receiving therapies in accordance to their genomic profiles | up to 4 weeks after biospecimen provision | 

 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, Foundation Medicine assays, Hepatocellular Cancer, Cholangiocarcinoma, Gallbladder Cancer, Pancreatic Cancer, Oesophageal Cancer, Stomach Cancer, Platform-Design, Biobanking