Patient-Derived Organoid-on-a-Chip Model for Personalized Prediction of Chemotherapy Efficacy in Pancreatic Cancer
A Study on the Consistency Between Patient-Derived Pancreatic Cancer Organoid-on-a-Chip Drug Sensitivity Test Results and Clinical Chemotherapy Efficacy
Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies worldwide, with a 5-year survival rate below 10%. Systemic chemotherapy is the mainstay of treatment for the majority of patients who present with unresectable disease. However, the objective response rates for standard first-line regimens, such as nab-paclitaxel plus gemcitabine (AG) and FOLFIRINOX, are only 15-30%. Currently, there are no validated predictive biomarkers to guide chemotherapy selection, leading to a trial-and-error approach that exposes patients to unnecessary toxicity and delays effective treatment.
Patient-derived organoids (PDOs) are three-dimensional in vitro models that recapitulate the genetic, histological, and phenotypic features of their source tumors. PDOs have shown promise as a functional precision medicine platform for predicting individual patient responses to anticancer therapies. Several retrospective and prospective studies across various tumor types have demonstrated high sensitivity and specificity for PDO-based drug sensitivity testing in predicting clinical outcomes. However, prospective data specifically focused on pancreatic cancer remain limited.
- Study Objective The primary objective of this study is to evaluate the concordance between PDO-based drug sensitivity test results and clinical efficacy in PDAC patients receiving standard first-line chemotherapy. Secondary objectives include optimizing culture conditions and drug testing protocols for pancreatic cancer PDOs derived from surgical and biopsy specimens.
Study Design This is a prospective, observational, multicenter cohort study. The study will enroll treatment-naïve patients aged 18-75 years with histologically confirmed PDAC who are scheduled to receive first-line chemotherapy. Fresh tumor tissue will be obtained from routine surgical resection or biopsy procedures. PDOs will be established from the collected specimens and subjected to in vitro drug sensitivity testing against the corresponding chemotherapy regimens. The testing results will be classified as "sensitive" or "insensitive" based on IC50 values and maximum inhibition rates.
Clinical treatment decisions will be made by the treating physicians according to standard guidelines and multidisciplinary team recommendations, independent of the PDO test results. Patients will be followed up every three treatment cycles with imaging assessments (CT or MRI) and laboratory evaluations. Clinical efficacy will be assessed using RECIST v1.1 criteria after six cycles or at the time of early surgery in the neoadjuvant setting. The concordance between PDO test results and clinical outcomes will be analyzed by calculating sensitivity, specificity, and overall accuracy.
- Study Population Approximately 164 patients will be screened to achieve 80 evaluable cases, accounting for a PDO culture success rate of 85%, a follow-up rate of 90%, and exclusions due to non-PDAC pathology or non-first-line treatment regimens. Eligible patients must have adequate organ and bone marrow function, an ECOG performance status of 0-2, and a life expectancy of at least 3 months. Exclusion criteria include inadequate sample quality, PDO culture failure, pregnancy, severe comorbidities, and unstable medical conditions.
- Study Sites This multicenter study is being conducted at six tertiary medical centers in China: Ruijin Hospital (Shanghai, lead site), Peking University Cancer Hospital, Beijing Friendship Hospital, The Second Hospital of Tianjin Medical University, The Second Xiangya Hospital of Central South University, and Shenzhen People's Hospital.
- Risks and Benefits This observational study poses no additional physical risk to participants, as samples are collected from residual tissue during routine diagnostic or therapeutic procedures. No investigational interventions are administered. Participants will not receive direct medical benefit from study participation; however, the findings may contribute to the development of a clinically applicable predictive tool to guide chemotherapy selection for future pancreatic cancer patients, potentially improving treatment outcomes and quality of life.
- Ethical Considerations The study will be conducted in accordance with the Declaration of Helsinki and applicable Chinese regulations. The protocol has been reviewed and approved by the institutional ethics committee. Written informed consent will be obtained from all participants prior to enrollment. All data will be anonymized and handled in strict compliance with privacy protection regulations.
- Timeline The study is planned from February 2026 to February 2028.
Descripción general del estudio
Estado
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Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Jiabin Jin, MD
- Número de teléfono: 0086-18917762352
- Correo electrónico: jjb11501@rjh.com.cn
Copia de seguridad de contactos de estudio
- Nombre: Zhaohong Wen, PhD
- Número de teléfono: 0086-13522210548
- Correo electrónico: wenzhaohong@daxiangbio.com
Ubicaciones de estudio
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Porcelana, 200025
- Reclutamiento
- Ruijin Hospital
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Contacto:
- Jiabin Jin, MD
- Número de teléfono: 0086-18917762352
- Correo electrónico: jjb11501@rjh.com.cn
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Age 18-75 years, both sexes
- Pathologically confirmed pancreatic ductal adenocarcinoma (PDAC) in treatment-naïve patients
- Ability to obtain sufficient fresh tumor tissue samples for organoid establishment through surgery or biopsy
- Planned to receive neoadjuvant therapy for borderline resectable disease, conversion therapy for locally advanced disease, or first-line therapy for metastatic disease, using single-agent or combination chemotherapy
- At least one measurable lesion per RECIST 1.1 criteria
- ECOG performance status 0-2
- Life expectancy ≥3 months
- Adequate organ and bone marrow function: hemoglobin ≥9.0 g/dL; absolute neutrophil count ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; total bilirubin ≤1.5×ULN (or ≤3×ULN with biliary obstruction); ALT/AST ≤2.5×ULN (or ≤5×ULN with biliary obstruction); serum creatinine ≤1.5×ULN or CrCl >60 mL/min
- Willing to sign informed consent, good compliance, and able to comply with follow-up
Exclusion Criteria:
- Sample quantity, quality, or preservation does not meet requirements
- Expected transport time >24 hours (including samples stored overnight before delivery)
- Organoid culture failure or testing quality control failure
- Inability to tolerate chemotherapy regimens
- Severe comorbidities, uncontrolled conditions, or active infections
- Pregnancy or breastfeeding
- History of severe autoimmune diseases
- Any unstable condition that may compromise patient safety or compliance
- Deemed unsuitable for inclusion by the investigator
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Pancreatic Cancer Patients Receiving First-Line Chemotherapy
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Concordance Between Organoid Drug Sensitivity Test Results and Clinical Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma Patients, Assessed by Sensitivity, Specificity, and Overall Accuracy
Periodo de tiempo: At the end of Cycle 6 (each cycle is 28 days), or at pre-surgery imaging for neoadjuvant patients; if death occurs before first post-treatment imaging, classified as ineffective.
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Concordance between organoid drug sensitivity test results and clinical chemotherapy efficacy in pancreatic ductal adenocarcinoma patients.
Organoid sensitivity is determined by exposing patient-derived organoids to chemotherapy regimens across 5-7 concentrations, measuring cell viability via ATP content, generating concentration-inhibition curves, and deriving IC50 values, with results classified as "sensitive" or "insensitive."
Clinical efficacy is assessed using RECIST v1.1 criteria after six treatment cycles, classifying outcomes as complete response, partial response, stable disease (with CA199 decrease or SDa) as effective, and stable disease (with CA199 increase or SDb) or progressive disease as ineffective.
Concordance is calculated as sensitivity, specificity, and overall accuracy using a four-fold table with 95% confidence intervals.
Unit of Measure: Percentage (%) - specifically, sensitivity (%), specificity (%), and overall accuracy (%).
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At the end of Cycle 6 (each cycle is 28 days), or at pre-surgery imaging for neoadjuvant patients; if death occurs before first post-treatment imaging, classified as ineffective.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Objective Response Rate (ORR) in Organoid-Sensitive vs. Insensitive Groups
Periodo de tiempo: Assessed at the end of Cycle 6 (each cycle is 28 days). For neoadjuvant patients, assessed at pre-surgery imaging. If death occurs before first post-treatment imaging, classified as non-responder.
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ORR is defined as the proportion of patients achieving best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. ORR will be calculated separately for the organoid-sensitive group and the organoid-insensitive group, and compared against the overall population to derive the ORR improvement rate in the sensitive group. Unit of Measure: Percentage (%) of patients. |
Assessed at the end of Cycle 6 (each cycle is 28 days). For neoadjuvant patients, assessed at pre-surgery imaging. If death occurs before first post-treatment imaging, classified as non-responder.
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Disease Control Rate (DCR) in Organoid-Sensitive vs. Insensitive Groups
Periodo de tiempo: Assessed at the end of Cycle 6 (each cycle is 28 days). For neoadjuvant patients, assessed at pre-surgery imaging. If death occurs before first post-treatment imaging, classified as non-responder.
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DCR is defined as the proportion of patients achieving best overall response of CR, PR, or stable disease (SD) per RECIST v1.1 criteria. DCR will be calculated separately for the organoid-sensitive group and the organoid-insensitive group. Unit of Measure: Percentage (%) of patients. |
Assessed at the end of Cycle 6 (each cycle is 28 days). For neoadjuvant patients, assessed at pre-surgery imaging. If death occurs before first post-treatment imaging, classified as non-responder.
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Progression-Free Survival (PFS) in Organoid-Sensitive vs. Insensitive Groups
Periodo de tiempo: Assessed every 3 treatment cycles (each cycle is 28 days) from treatment initiation until disease progression or death from any cause, with primary analysis time points at 6 months and 12 months post-treatment initiation.
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PFS is defined as the time from treatment initiation to the first documented disease progression per RECIST v1.1 criteria or death from any cause, whichever occurs first. Patients alive without progression at the time of analysis will be censored at the last valid tumor assessment. PFS curves will be estimated using the Kaplan-Meier method, and PFS distribution will be compared between the organoid-sensitive and organoid-insensitive groups using the log-rank test. Unit of Measure: Months (from treatment initiation to event). |
Assessed every 3 treatment cycles (each cycle is 28 days) from treatment initiation until disease progression or death from any cause, with primary analysis time points at 6 months and 12 months post-treatment initiation.
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Colaboradores e Investigadores
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Palabras clave
Otros números de identificación del estudio
- DX-PDAC-01
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Información sobre medicamentos y dispositivos, documentos del estudio
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