PTC in Personalizing Neoadjuvant Therapy for Patients With Advanced Gastrointestinal Tumor

Study Overview
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Brief Summary
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To explore the value of PTC drug screening technique in selecting neoadjuvant therapy for advanced gastrointestinal cancer.

Detailed Description
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In this study, patients diagnosed with advanced gastrointestinal cancer including locally advanced gastric cancer, locally advanced colorectal cancer and colorectal cancer with liver metastasis. Tumor sample will be collected by endoscopy biopsy, needle biopsy or surgery, which will used for PTC drug screening. Patients will be randomized to two groups. Patients in experiment group will receive neoadjuvant therapy based on PTC drug screening, and patients in control group will receive neoadjuvant therapy based on clinical experience. 2-4 cycles of neoadjuvant therapy will be administered. Patients appropriate for surgery will receive radical surgery after neoadjuvant therapy. Pathological response will be compared primarily between these two groups. This is a randomized controlled, open-label and sequential designed clinical trial. All neoadjuvant therapy used in this study or for PTC drug screening comply with NCCN (National comprehensive cancer network) or CSCO (Chinese Society of Clinical Oncology) guidelines.

Official Title
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Patient-derived Tumor-like Cell Clusters (PTC) in Personalizing Neoadjuvant Therapy for Patients With Advanced Gastrointestinal Tumor: A Prospective, Open-label and Randomized Study

Conditions
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Gastrointestinal Neoplasms

Intervention / Treatment
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* Other: PTC drug screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed of gastrointestinal adenocarcinoma by biopsy existence of initially resectable lesions evaluated by investigators indications of neoadjuvant chemotherapy including: 1) locally advanced gastric cancer cT1-2N1-3M0 & cT3-4N0-3M0; 2) locally advanced colorectal cancer cT3-4 or N+; 3)colorectal carcinoma with synchronous liver metastases: CRS≤2; 4)other patients who are considered to be appropriate to receive neoadjuvant chemotherapy determined by MDT never receive any tumor related treatment including chemotherapy, radiotherapy, and immune therapy never diagnosed of other malignancies able to tolerate chemotherapy ECOG≤2 life expectance >6 months at least 1 measurable lesions(according to RECIST 1.1) informed consent Exclusion Criteria: pregnant or lactating women participating in other clinical trials within 6 months MSI-H or dMMR or EBER(+) lesion located within 10cm from anal margin severe liver dysfunction severe renal dysfunction cognitive disorder, mental disease or poor compliance allergic to known chemotherapeutic agents other conditions not suitable to participate in this trial determined by investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant therapy based on PTC drug screening<br>Patients will receive neoadjuvant therapy based on PTC drug screening. The regimen is complied with NCCN and CSCO guidelines. PD-1 inhibitor will be used if effective in drug screening. | Other: PTC drug screening<br>* PTC is an in vitro tumor model, which serves as a structural and functional unit recapitulating the original tumors in genotype, phenotype, and drug response. PTC will be used in drug screening.<br>|
| No Intervention: Neoadjuvant therapy based on clinical experience<br>Patients will receive neoadjuvant therapy based on clinical experience. The regimen is complied with NCCN and CSCO guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete response rate(pCR) | having no invasive cancer left in the resected sample | immediately evaluated after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological response rate | tumor regression grade 0-2 | immediately evaluated after surgery | 
| objective response rate(ORR) | CR+PR according to RECIST 1.1 | evaluated by imaging before surgery | 
| disease control rate(DCR) | CR+PR+SD according to RECIST 1.1 | evaluated by imaging before surgery | 
| R0 resection rate | microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed | immediately evaluated after surgery | 
| prediction accuracy of PTC | consistency between the effect of neoadjuvant chemotherapy and the result of PTC assay | immediately evaluated after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant, chemotherapy