Neoplasms

Digestive System Diseases

All Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Stomach Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Pancreatic Neoplasms

Biliary Tract Neoplasms

Gastrointestinal Stromal Tumors

Neuroendocrine Tumors

Esophageal Squamous Cell Carcinoma

Neoplasms, Unknown Primary

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Biliary Tract Diseases

Neoplasm Metastasis

Neoplastic Processes

Stomach Cancer

Pancreatic Cancer

Neuroendocrine Tumor

Neuroepithelioma

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Angiogenesis Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

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.

FGFR Inhibitor, IDH1 Inhibitor, HER2 Inhibitor, PARP Inhibitor, BRAF Inhibitor, MEK Inhibitor, ICIs, EGFR-TKIs, NTRK-TKI, and et. al.

Patients will receive other treatments, including cytotoxic drugs, antiangiogenic drugs, best supportive care, clinical trials of unmatched new drugs, etc..

Other Therapy

Lin Shen, MD

Shen Lin, MD

Shen Lin, professor

This a prospective real-world navigation study using tumor DNA sequencing technology to sequence genes of previously treated and refractory gastrointestinal tumors, which are generally considered to be highly heterogeneous and complex, to screen potential molecular targeted drugs for individualized treatment. This study may provide feasibility and response information, which will be the basis for designing better randomized trials, which may change the pattern of cancer treatment. If the hypothesis is finally proved, it will help doctors and molecular biologists to choose the best drug (or combination of drugs) based on the individual oncogenomics of each patient.

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.

Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics

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

Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment

Proportion of patients with intervening genomic variation

Progression Free Survival (PFS) per RECIST 1.1 criteria according to investigators assessment

Overall Survival (OS) per RECIST 1.1 criteria according to investigators assessment

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Differences of OS between 2 groups per RECIST 1.1 criteria according to investigators assessment

Hangzhou DIAN Medical Diagnostic Center Co., Ltd., China

Peking University

Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics	NCT04584008	Biliary Tract N... Gastric Cancer Esophageal Squa... Colorectal Canc... Gastrointestina... Pancreatic Canc... Neuroendocrine ... Unknown Primary... Digestive Cance...	FGFR Inhibitor,... Other Therapy	18 Years -	Peking University
Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics	NCT04584008	Biliary Tract N... Gastric Cancer Esophageal Squa... Colorectal Canc... Gastrointestina... Pancreatic Canc... Neuroendocrine ... Unknown Primary... Digestive Cance...	FGFR Inhibitor,... Other Therapy	18 Years -	Peking University

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