Solid Tumor Cancer, Solid Tumor Malignancies
Conditions
Brief summary
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.
Interventions
OTHERPDTF-Guided Personalized Treatment
Patients 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.
Sponsors
Qilu Hospital of Shandong University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria simultaneously to be eligible for enrollment. All criteria must be confirmed through clinical evaluation, laboratory tests, and imaging during the screening period, and approved in writing by the principal investigator. 1. Age between 18 and 75 years (inclusive), regardless of gender. 2. 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. 3. 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. 4. No prior systemic treatment, or disease progression or recurrence more than 6 months after previous neoadjuvant/adjuvant chemotherapy. 5. ECOG performance status of 0-1, ensuring the patient can tolerate biopsy and treatment. 6. Expected survival of at least 3 months, with no severe concomitant diseases affecting trial participation. 7. Adequate organ function, including: * Bone marrow function: Hemoglobin ≥80 g/L; Neutrophil count ≥1.5×10\^9/L; White blood cell count ≥3.5×10\^9/L; Platelet count ≥100×10\^9/L; * Liver function: Serum total bilirubin ≤1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤3×ULN, or ≤5×ULN in patients with liver metastases; * Renal function: Serum creatinine ≤1.5×ULN, or creatinine clearance (CrCl) ≥60 mL/min (calculated using the Cockcroft-Gault formula); * Cardiac function: New York Heart Association (NYHA) classification \< III; Left ventricular ejection fraction (LVEF) ≥50%. 8. Women of childbearing potential must use reliable contraception or have a negative pregnancy test (serum or urine) within 7 days prior to enrollment, and be willing to use appropriate contraception during the trial and for 8 weeks after the last dose of the study drug. Men must also agree to use appropriate contraception during the trial and for 8 weeks after the last dose of the study drug. 9. Voluntary participation in the study, signed informed consent form, good compliance, and willingness to cooperate with follow-up, including providing biological samples for PDTF construction and future research.
Exclusion criteria
Patients meeting any of the following criteria are ineligible for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Until 3 months after the last patient is enrolled | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Until 12 months after the last patient is enrolled | 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 | Until 1 month after the last patient is enrolled | Percentage of patients for whom PDTF model establishment and drug screening are successfully completed |
| Disease Control Rate (DCR) | Until 3 months after the last patient is enrolled | 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). |
| Treatment-Related Adverse Events | Until 12 months after the last patient is enrolled | Number and percentage of patients experiencing treatment-related adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, 5.0). Adverse events will be summarized by type, frequency, and severity (Grade 1-5). |
| Biopsy-Related Complications | Until 12 months after the last patient is enrolled | Number and percentage of patients experiencing complications related to tumor biopsy procedures performed for PDTF model establishment (e.g., bleeding, infection, pain requiring intervention, pneumothorax, or other procedure-related adverse events), graded using NCI CTCAE 5.0. |
| Time to PDTF-Guided Treatment | Until 1 month after the last patient is enrolled | Time from receipt of tumor tissue to finalization of a PDTF-guided treatment recommendation |
Countries
China
Contacts
Primary ContactLian Liu, M.D., Ph.D.
Backup ContactJiahui Chu, Ph.D.
Outcome results
None listed