iCAGES-guided Precision Therapy for Cancers in Contrast to Standard Care or IHC-guided Theray

Study Overview
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Brief Summary
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This study prospectively evaluates whether the use of iCAGES (integrated CAncer GEnome Score) tool in guiding the treatment of advanced cancers is superior to current standard care or IHC-guided therapy in progress free survival (PFS),overall survival (OS),and improvement of life quality.

Detailed Description
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Cancer is a fatal disease caused by the accumulation of various oncogene and tumor suppressor gene mutations. Studies of high-throughput sequencing for patients who suffered from cancer has found that different mutations play a different role in the occurrence and development of different cancers. Several gene panels already exist to help identify mutations in a few genes that may have corresponding FDA-approved drugs or drugs under clinical trials. However, given whole-genome/exome sequencing data, the suitable clinical analysis tool to analyze individualized cancer-related gene mutations, and recommend the most appropriate targeted treatment options among hundreds of possible drugs therapy is absent currently. The recently proposed iCAGES is a precise biomedical informatics analysis tool, which could help increase the accuracy of cancer driver gene detection and prioritization, bridge the gap between personal cancer genomic data and prior cancer research knowledge,and facilitate cancer molecular diagnosis as well as personalized precision therapy. IHC detection of multiple molecules such as EGFR, HER2-3, TROP3, NECTIN4, MET, B7-H3-4, B1-H7, Claudin18.2, FGFR1-4, Mesothelin, ROR1, BCMA, AXL, TF, FRα, CD70, PPARα, HIF-2α, RET, ROS1, NTRK, CDK4/6, FLT3, EZH2 are also scheduled for appropriate targeted therapy and comparison if available.

Official Title
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Multicentre Perspective Non-interventional Study of Survival Benefits of iCAGES-guided Therapy in Contrast to Standard Therapy or IHC-guided Therapy for Advanced Cancers

Conditions
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Lung Cancer, Gene Abnormality, Gene Product Sequence Variation, Cancer

Intervention / Treatment
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* Drug: inhibitors, ADC drugs such as tarceva, capmatinib, padcev et al for A/C group.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological and clinical diagnosis of recurrence / metastatic lung cancer or other advanced cancers. There are PACS images available at the Second Affiliated Hospital of Guangzhou Medical University and the collaborated Hospitals. The patient is informed consent and signed a written consent. Exclusion Criteria: Age > 70 or <18 years old. Previous history of malignant tumors. Pregnant or lactating female patients. Any serious concomitant disease that is expected to have an adverse effect on prognosis, including the heart disease that treatment is required, unsatisfactory controlled diabetes and psychiatric disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Study group (A group)<br>In this group, we perform whole exome or genome sequencing of tumor sample in compared to blood sample, screen tumor-related special mutations by using biomedical informatics analysis procedure and utilized the iCAGES system to rank the most appropriate drugs available and then manually examine this list to select the best therapeutic strategy for the patient based on availability of drug and expert knowledge. The PFS, OS, and quality of life (QOL) will be recorded and compared with that from standard care. | Drug: inhibitors, ADC drugs such as tarceva, capmatinib, padcev et al for A/C group.<br>* Choose appropriate targeted drugs according to NGS/IHC results.<br>|
| Control group (B group)<br>In this group, patients with advanced cancers (matched with Group A) will be treated under the guidance of NCCN, without performing iCAGES analysis. | |
| Control group (C group)<br>In this group, patients with advanced cancers (matched with Group A) will be treated with appropriate targeted drugs according to IHC detection of more than 20 protein molecules with blank tissue slides from the cancer. | Drug: inhibitors, ADC drugs such as tarceva, capmatinib, padcev et al for A/C group.<br>* Choose appropriate targeted drugs according to NGS/IHC results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | The PFS will be recorded during the follow up time. | 2 years | 
| OS | The OS will be recorded during the follow up time. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life. | Physicians Global Assessment to measure quality of life | 2 years | 
| Pain | Visual Analog Score for pain | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IHC, lung cancer, iCAGES, gene mutation, precision medicine, advanced cancers, Targeted therapy