- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04584008
Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics (VISIONARY)
A Real-world Study to Explore and Evaluate Individualized Targeted Agents for Patients of Digestive Cancers Based on Molecular Characteristics After Standard Therapy Failure in China
Study Overview
Status
Conditions
Detailed Description
This is a prospective, open label, real-world study to evaluate the feasibility of matched molecular targeted therapy in patients with refractory gastrointestinal cancer based on tumor molecular characteristics as standard treatment failure. This is a non-randomized trial designed to test molecular matching strategies based on patient genome information. The molecular tumor board (MTB) will recommend treatment, but the treatment decision is up to the attending physician. FoundationOne CDx was used for tissue genomic analysis. If possible, PD-L1 immunohistochemistry (IHC), tumor mutation load (TMB), and microsatellite instability (MSI) status will also be evaluated. Based on this information, MTB, composed of multidisciplinary experts, will focus on the selection of customized, best matched drugs or combinations to target most of the genomic changes in each patient, also taking into account potential drug toxicity. The final treatment will be based on the choice of oncologists, who will formulate treatment plan by combining MTB discussion, patient preference, attention to complications, consideration of drug toxicity, insurance coverage of off label drugs and availability of clinical trials of research drugs, thus reflecting the actual clinical practice nowadays in China. The acquisition of drugs follows the actual situation in the real world and is not within the scope of this study design.
The principles of MTB treatment recommendations can be referred to the NCI-MATCH trial:
Grade 1: FDA / NMPA approval; clear evidence and mechanism; concomitant diagnostic relationship between drug and target.
Grade 2: The drug reaches the clinical end point (objective response rate, PFS or OS); there is evidence of target inhibition; there is strong evidence to predict relationship between the target and the drug.
Grade 3: The drug has evidence of clinical activity and target inhibition; there is some evidence to predict the relationship between target and drug.
Grade 4: Pre-clinical evidence of anti-tumor activity and evidence of target inhibition; there is hypothesis to predict the relationship between target and drug.
Patients who meet the inclusion criteria and sign informed consent will be analyzed for tumor mutation by FoundationOne CDx detection. Biopsy specimens of metastatic foci can be selected for gene detection. If there is no targeted therapy among patients, the archived diagnostic tumor samples can also be used for detection. If the patient has received targeted therapy, the investigators will try to obtain biopsy samples after treatment. If the sample cannot be tested or the test results are not satisfactory, additional slices need to be sent to the laboratory. If the repeated test fails, repeat biopsy if the clinical conditions permit, or patients should be included in the unmatched treatment group.
Determining the interventability of gene mutations depends on genomic changes, allele frequency, and diagnosis. This study will combine the recommendations of MTB and gene testing reports to determine the interventability of mutated genes.
Interventional mutation: cancers have FDA or NMPA approved therapies, or there are matching drugs in clinical trials.
Non-interventional mutation: there is no FDA or NMPA approved treatment for cancers, and no matching drug is available in clinical trials.
MTB should at least be composed of attending doctors, molecular pathology experts and bioinformatics experts. The research center is responsible for the establishment and holding of MTB. As management of patients enrolled in this study is essential, the research committee, including but not limited to the main investigator of the study and the treated medical oncologist, can provide advice as needed between MTB meetings to avoid treatment delays. By analyzing the genomic variation of patients, independent MTB recommends molecular targeted therapy that can inhibit the mutation directly or through related pathways or be included in relevant clinical trials. The independent research committee will use the "N-to-1" model of precision medicine to propose a matching therapy consisting of at least one drug that targets molecular changes. The investigators expect 50-70% of patients to carry intervening variants, and that proportion is rising rapidly as learning more about these pathways and drugs. The investigators expect that about 40% of patients with intervening variants will be able to receive molecular targeted "matching" therapy.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lin Shen, MD
- Phone Number: 86-10-88196561
- Email: linshenpku@163.com
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100142
- Recruiting
- Peking University Cancer Hospital
-
Contact:
- Shen Lin, MD
- Phone Number: 010-88196561
- Email: Linshenpku@163.com
-
Principal Investigator:
- Shen Lin, professor
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Histologically confirmed recurrent or metastatic malignant tumors of digestive tract, including but not limited to:
- Biliary tract cancer (including gallbladder cancer and cholangiocarcinoma)
- Gastric cancer
- Esophageal squamous cell carcinoma
- Colorectal cancer
- Gastrointestinal stromal tumor
- Pancreatic cancer
- Primary unknown metastatic carcinoma of digestive system
- failure of conventional treatment;
- have at least one measurable lesion according to RESIST1.1;
- the target lesion is not suitable for local treatment;
- the expected survival time was more than 3 months;
- age ≥ 18 years old;
- the main organs function well;
- be able to swallow and retain oral medication if necessary;
- patients must have enough tissue samples for gene mutation detection;
- informed consent signed.
Exclusion Criteria:
- main lesions were suitable for local treatment;
- serious or uncontrolled medical diseases that researchers consider to be confusing in the treatment response analysis (i.e. uncontrolled diabetes, chronic kidney disease, chronic lung disease or uncontrolled active infection, mental illness / social status that limits compliance with research requirements);
- pregnant or lactating patients or any fertile patients taking no appropriate pregnancy prevention.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Matched Targeted Agent
|
According to the treatment dose approved by NMPA/FDA, evaluation will be conducted every 2 cycles until tumor progression or adverse events cannot be tolerated.
Other Names:
|
Active Comparator: Unmatched Therapy
|
Patients will receive other treatments, including cytotoxic drugs, antiangiogenic drugs, best supportive care, clinical trials of unmatched new drugs, etc..
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR) of patients receiving targeted agent
Time Frame: up to 2 years
|
Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment
|
up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with intervening genomic variation
Time Frame: up to 2 years
|
Proportion of patients with intervening genomic variation
|
up to 2 years
|
Progression Free Survival (PFS) of patients receiving targeted agent
Time Frame: up to 2 years
|
Progression Free Survival (PFS) per RECIST 1.1 criteria according to investigators assessment
|
up to 2 years
|
Overall Survival (OS) of patients receiving targeted agent
Time Frame: up to 2 years
|
Overall Survival (OS) per RECIST 1.1 criteria according to investigators assessment
|
up to 2 years
|
Number of participants with treatment-related adverse events
Time Frame: up to 2 years
|
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
|
up to 2 years
|
Differences of OS between 2 groups
Time Frame: up to 2 years
|
Differences of OS between 2 groups per RECIST 1.1 criteria according to investigators assessment
|
up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Lin Shen, MD, Peking University Cancer Hospital & Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neoplastic Processes
- Esophageal Diseases
- Biliary Tract Diseases
- Neoplasms, Connective Tissue
- Neoplasm Metastasis
- Neoplasms, Squamous Cell
- Carcinoma, Squamous Cell
- Esophageal Neoplasms
- Gastrointestinal Stromal Tumors
- Gastrointestinal Neoplasms
- Esophageal Squamous Cell Carcinoma
- Neuroendocrine Tumors
- Neoplasms, Unknown Primary
- Biliary Tract Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Poly(ADP-ribose) Polymerase Inhibitors
Other Study ID Numbers
- NGS01
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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