This is a prospective, single-arm, open-label, exploratory clinical trial conducted at Qilu Hospital of Shandong University. Approximately 35 patients with advanced or metastatic refractory cancers will be enrolled. Fresh tumor or metastatic biopsy samples will be collected to establish patient-derived tumor tissue fragment models (PDTFs). Each PDTF will be validated for histologic, molecular, and genetic homology with the original tumor, followed by high-throughput ex vivo drug sensitivity testing using chemotherapy, targeted agents, or immunotherapy drugs and recommended by clinical guidelines.
This study aims to demonstrate that the PDTF platform can serve as a rapid, reliable, and clinically relevant tool for precision therapy development and clinical decision-making in refractory cancers, potentially bridging translational models and individualized clinical care.
Age between 18 and 75 years (inclusive), regardless of gender.
Confirmed diagnosis of refractory malignant tumors via pathological biopsy, including locally advanced unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma; confirmed as stage IV (advanced, recurrent, or metastatic) according to international TNM staging; patients with highly suspected gene mutations or requiring reconfirmation of molecular pathological diagnosis; or patients previously treated at this institution who have obtained pathological samples and completed PDTF construction but have progressed to refractory tumors.
At least one measurable lesion according to RECIST v1.1 criteria; the lesion is expected to be sufficiently large (diameter greater than 2 cm), such that tissue collection does not affect pathological diagnosis or other clinical treatment needs, and residual tissue samples from pathological testing can be used to construct the PDTF model.
No prior systemic treatment, or disease progression or recurrence more than 6 months after previous neoadjuvant/adjuvant chemotherapy.
No lesions available for biopsy, or concurrent or metachronous multiple primary malignant tumors, to avoid interference with efficacy evaluation.
Severe dysfunction of liver, kidney, heart, or other vital organs (e.g., Child-Pugh class C liver failure, NYHA class III-IV heart failure, creatinine clearance <30 mL/min).
Poor compliance, or contraindications to chemotherapy, targeted drugs, or immunotherapy (e.g., history of severe allergies); allergy to any study drug or its excipients, severe allergy history, or contraindications to the study drug.
Uncontrolled cardiovascular or cerebrovascular events, such as: NYHA class ≥2 heart failure; unstable angina; myocardial infarction within 1 year; clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; cerebral hemorrhage or infarction (excluding asymptomatic lacunar infarcts not requiring treatment); severe cardiovascular or cerebrovascular events within 12 months; uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg despite monotherapy); history of arterial thrombosis or deep vein thrombosis within 6 months prior to enrollment, or history of bleeding tendency or bleeding within 2 months prior to enrollment, regardless of severity; stroke or transient ischemic attack within 12 months prior to enrollment.
Single group
PDTF-Guided Personalized Treatment
Other interventionPatients with refractory solid tumors in this arm will undergo drug sensitivity testing using patient-derived tumor tissue fragment (PDTF) models. Fresh tumor tissues obtained from biopsy or surgery will be processed to establish PDTF models that preserve the original tumor architecture and microenvironment. Each PDTF will be exposed ex vivo to a panel of anti-cancer agents, including chemotherapy, targeted therapies, and/or immunotherapy drugs. Based on the PDTF drug response profiles, an individualized treatment regimen will be formulated after obtaining the sensitivity results. Patients will then receive the PDTF-guided regimen until disease progression, unacceptable toxicity, death, or withdrawal of consent. Clinical outcomes and concordance between PDTF sensitivity and in-vivo treatment response will be assessed.
PDTF-Guided Personalized Treatment
Other interventionPatients with refractory solid tumors in this arm will undergo drug sensitivity testing using patient-derived tumor tissue fragment (PDTF) models. Fresh tumor tissues obtained from biopsy or surgery will be processed to establish PDTF models that preserve the original tumor architecture and microenvironment. Each PDTF will be exposed ex vivo to a panel of guideline-recommended, FDA- or NMPA-approved anti-cancer agents, including chemotherapy, targeted therapies, and/or immunotherapy drugs. Based on the PDTF drug response profiles, an individualized treatment regimen will be formulated within 24 hours after obtaining the sensitivity results. Patients will then receive the PDTF-guided regimen until disease progression, unacceptable toxicity, death, or withdrawal of consent. Clinical outcomes and concordance between PDTF sensitivity and in-vivo treatment response will be assessed.
Objective Response Rate (ORR)
Proportion of patients achieving a best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. CR is defined as disappearance of all target lesions and normalization of tumor markers. PR is defined as at least a 30% decrease in the sum of diameters of target lesions compared with baseline.
Disease Control Rate (DCR)
Proportion of patients whose best overall response is complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Progression-Free Survival (PFS)
Time from first dose of PDTF-guided treatment to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Feasibility of PDTF-Guided Treatment
Percentage of patients for whom PDTF model establishment and drug screening are successfully completed
Time to PDTF-Guided Treatment
Time from receipt of tumor tissue to finalization of a PDTF-guided treatment recommendation
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