Evaluation of Efficacy of Comprehensive Genomic Tumour Profiling (CGP) From Liquid and/or Tissue Biopsy in Patients With Locally Advanced and/or Metastatic Carcinoma

Study Overview
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Brief Summary
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The aims of this study are to evaluate the efficacy of comprehensive genomic tumour profiling (CGP) from liquid and/or tissue biopsy in patients with locally advanced and/or metastatic carcinoma. to evaluate and describe the impact of treatment decisions based on CGP on individual progression free survival in patients with locally advanced and/or metastatic carcinoma to evaluate and describe similarities and differences between the treatment suggestions based on CGP/IHC (immuno-histochemistry) of tissue biopsy and liquid biopsy. In patients with locally advanced and/or metastatic carcinoma the primary efficacy objective of the study is, to observe and describe the PFS (progression-free survival) of the matched treatment compared to the PFS of the most recent therapy.

Detailed Description
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The SOUND study will be exploring the treatment rates and outcomes of CGP-driven targeted treatment in patients with advanced or metastasized cancer. It will use a substantially larger gene-panel than previous studies in Austria. Departing from the routine clinical practice, study patients will have the opportunity to have CGP from liquid and/or tissue biopsy. The treatment decision will be discussed within a molecular tumour board consisting of experts in clinical oncology, human genetics and pathology. The treatment decision process will be supported and documented by a software. Data from the SOUND study will cover the whole analysis process, the reasons for the treatment decision, reasons for getting or not-getting a matched treatment as well as the outcome, treatment and hospitalisation costs. The SOUND study will give valuable insights into the clinical practice of CGP-driven therapy in Austria and describe the experience and the possible restrictions. Considering the differing conditions in Austria, the SOUND study will generate data that might be useful for best practice sharing with other countries in the future.

Official Title
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Evaluation of Efficacy of Comprehensive Genomic Tumour Profiling (CGP) From Liquid and/or Tissue Biopsy in Patients With Locally Advanced and/or Metastatic Carcinoma

Conditions
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Locally Advanced Carcinoma, Metastatic Cancer

Intervention / Treatment
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* Diagnostic Test: Next Generation Sequencing
* Diagnostic Test: Next Generation Sequencing
* Genetic: Biomarker Monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Initial diagnosis of histologically confirmed locally advanced and/or metastatic carcinoma Radiologically confirmed progression under the most recent therapy No further evidence-based drug treatment is established, or no satisfactory alternative treatments are available for the locally advanced and/or metastasized carcinoma Further therapy is medically feasible ECOG (Eastern Cooperative Oncology Group) performance status 0-2 Life expectancy of at least 12 weeks Written informed consent and willingness to cooperate during the course of the study Capability to understand the intention and the consequences of the study Exclusion Criteria: Untreated CNS (central nervous system) metastases. Patients with treated CNS metastases are eligible if they are clinically stable with regard to neurologic function Pregnant or breast feeding Other malignomas, diagnosed < 5a before inclusion (except localized squamous cell carcinomas of the skin, surgically curable melanomas of the skin, basal cell carcinomas of the skin)

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: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Open, Prospective, Multicentre IVD (in vitro diagnostic device) Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult patients with locally advanced and/or metastasized carcinoma<br>Liquid biopsies of all 200 study patients will be analysed with FoundationOne®Liquid CDx. Tissue biopsies from all study patients for whom a tissue biopsy is available will be analysed with FoundationOne® CDx and IHC (approximately 50% of the enrolled patients). Biomarker Monitoring of study patients receiving matched therapy with AVENIO ctDNA Surveillance Kit. | Diagnostic Test: Next Generation Sequencing<br>* Molecular analysis of liquid biopsy.<br>* Other names: FoundationOne®Liquid CDx;Diagnostic Test: Next Generation Sequencing<br>* Molecular analysis of tissue biopsy.<br>* Other names: FoundationOne® CDx;Genetic: Biomarker Monitoring<br>* Biomarker Monitoring of study patients receiving matched therapy.<br>* Other names: AVENIO ctDNA Surveillance Kit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Progression Free Survival (PFS): (matched therapy) /PFS (most recent therapy) > 1.3 | To observe and describe the PFS of the matched treatment compared to the PFS of the most recent therapy, PFS = number of calendar days from start treatment to progression of disease | Start of treatment to radiomorphologically confirmed progression of disease, that is on average about 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of potentially actionable targets | To evaluate the number of targets identified with NGS (next-generation sequencing) and IHC, that are potentially actionable with an approved drug on-label, off-label or an experimental drug per patient | Within seven days after NGS report at Molecular Tumour Board, i.e. 14 to 30 days after enrolment of patient | 
| Proportion of patients with potentially actionable targets | To investigate the proportion of patients with targets actionable by an approved drug on-label, off-label or an experimental drug. | A maximum of 30 months after first patient first visit | 
| Calendar days from enrolment into the study to the date of death or last visit alive | To observe and describe overall survival (OS) | Enrolment to death or last visit alive, that is on average about 8 months | 
| Proportion of patients with best overall response of either complete response (CR) or partial response (PR), based on their overall response | To observe and describe objective response rate (ORR), Response will be evaluated by the investigator as defined by RECIST 1. or irRECIST | A maximum of 30 months after first patient first visit | 
| Proportion of patients with successful molecular profiling from liquid or tissue biopsy, in whom a matched therapy was recommended | To investigate the proportion of patients with successful molecular profiling | A maximum of 30 months after first patient first visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Comprehensive Genomic Tumour Profiling, Targeted Therapy, Progression Free Survival, Next Generation Sequencing, Molecular Tumour Board, Tumour-specific Therapy