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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Lung Cancer; Gene Product Sequence Variation; Gene Abnormality
• Intervention / Treatment: Drug: inhibitors, ADC drugs such as tarceva, capmatinib, padcev et al for A/C group.

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Zhenfeng Zhang, MD,PhD; Phone Number: +86-020-34153532; Email: zhangzhf@gzhmu.edu.cn
• Study Contact Backup: Name: Deji Chen, MD,PhD; Phone Number: +86-020-34153532; Email: chendeji2003@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • Recruiting
      • The Second Affiliated Hospital of Guangzhou Medical University
      • Contact: Zhenfeng Zhang, MD,PhD; Phone Number: +86-020-34153532; Email: zhangzhf@gzhmu.edu.cn
      • Principal Investigator: Jiexia Zhang, MD,PhD
      • Principal Investigator: Ming Zhao, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

In this study, all the patients will be recruited from the Second Affiliated Hospital of Guangzhou Medical University and the collaborated Hospitals during 01/07/2017 to 01/07/2019, 250 advanced patients (90 cases for A group, 70 cases for B group, and 90 cases for C group) are anticipated to be collected. All the patients are more than 18 years old and less than 75 years old. The follow-up will be performed every 2 month until 2 years after the first treatment post-recruitment or quit.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group (A group); 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.; Choose appropriate targeted drugs according to NGS/IHC results.
Control group (B group); 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); 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.; Choose appropriate targeted drugs according to NGS/IHC results.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Collaborators: Sun Yat-sen University; The First Affiliated Hospital of Guangzhou Medical University
• Investigators: Principal Investigator: Zhenfeng Zhang, MD,PhD, Second Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Dong C, Guo Y, Yang H, He Z, Liu X, Wang K. iCAGES: integrated CAncer GEnome Score for comprehensively prioritizing driver genes in personal cancer genomes. Genome Med. 2016 Dec 22;8(1):135. doi: 10.1186/s13073-016-0390-0.

Helpful Links

• test link

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: June 15, 2017
• First Submitted That Met QC Criteria: June 17, 2017
• First Posted (Actual): June 20, 2017

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: lung cancer; Targeted therapy; precision medicine; advanced cancers; IHC; gene mutation; iCAGES
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: ZZiCAGES-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes