Patient Derived Organoids (PDOs) to Observe the Clinical Consistency of Personalized Neoadjuvant Therapy for Resectable Esophageal Squamous Cell Carcinoma

NCT ID: NCT07054086

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-03-01
• Study Completion Date: 2026-07-31

Brief Summary

Study Title:

Observing Clinical Consistency of Personalized Neoadjuvant Therapy Using Patient-Derived Organoid Models (PDO) in Resectable Esophageal Squamous Cell Carcinoma

Goal:

This study aims to explore whether patient-derived organoid models (PDO)-miniature tumors grown from patients' tissue samples-can accurately predict how individuals respond to personalized pre-surgery treatments (neoadjuvant therapy) for esophageal squamous cell cancer (ESCC). The study will compare results from drug sensitivity tests performed on PDO models with actual clinical outcomes after treatment to assess consistency and potential as a predictive tool.

Main Questions Addressed:

Do PDO models accurately reflect patients' tumor characteristics and response patterns to chemotherapy/immunotherapy combinations? Can PDO drug sensitivity testing reliably predict clinical responses (treatment effectiveness) in patients receiving personalized neoadjuvant therapy?

Study Design:

This observational study will enroll patients diagnosed with resectable ESCC who undergo standard neoadjuvant therapy (chemotherapy +/- immunotherapy) before surgery. No treatments will be assigned by the study-therapy decisions remain in physicians' discretion based on standard care protocols.

Participant Procedures:

Patients will provide tissue samples (via endoscopy) used to grow PDO models and blood samples (optional) to study immune cell interactions with tumors. These samples will enable labs to test drug responses in vitro ("lab-on-a-chip" models) while patients proceed with their standard-of-care treatments and surgeries.

Key Activities:

Lab Work (non-invasive procedures post-endoscopy/surgery):

PDO models grown from tumor tissue samples (culturing process) will mimic patients' tumors in miniature (preserving biological features).

Drug sensitivity testing (chemotherapy agents like paclitaxel, platinum drugs and immunotherapies targeting PD-1/PD-L1 pathways**) will assess how tumors respond (growth inhibition rates).

Immune cell interactions (from blood samples) will model tumor-immune microenvironment responses to treatments (immunotherapy relevance).

Clinical Follow-Up:

Patients will undergo standard-of-care treatments (therapy decisions made independently) and regular monitoring post-treatment (survival follow-up every 3 months, adverse events tracked during therapy, clinical response evaluated per RECIST criteria).

Duration:

Study participation involves tissue/blood sample collection (during standard diagnostic procedures) followed by routine clinical care monitoring (treatment duration, post-surgery follow-up). Total study timeline spans March-December 2025 (1 year) with participant recruitment beginning February 2025.

Ethical Considerations:

Participants provide informed consent acknowledging optional blood sample collection (if needed) and understand study aims.

Patient identifiers removed from samples/test results ensuring confidentiality (ethical compliance).

No financial or treatment incentives-participation voluntary (patients retain autonomy) including withdrawal at any time (without affecting clinical care decisions).

Study Significance:

By bridging lab models with real-world treatment responses (PDOs validated against clinical outcomes), this research aims to develop personalized treatment strategies (precision oncology) reducing trial-and-error prescribing patterns (currently observed discrepancies in neo-adjuvant therapy responses among ESCC patients).

Conditions

Esophageal Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Case-group

Neoadjuvant Chemotherapy (NACT)

Intervention Type: DRUG

The planned regimen for neoadjuvant therapy may include one or more of the following agents:

1. Paclitaxel Injection

2. Albumin-bound paclitaxel Injection (Abraxane® equivalent formulation)

3. Cisplatin Injection

4. Carboplatin Injection

5. Nivolumab

6. Pembrolizumab

7. Toripalimab

8. Tirilibumab

9. Camrelizumab The specific agent(s) and their combination will be selected based on the patient's clinical treatment protocol. The final regimen must be approved jointly by the principal investigator and the attending physician according to established clinical guidelines and individualized patient factors.

Interventions

Neoadjuvant Chemotherapy (NACT)

The planned regimen for neoadjuvant therapy may include one or more of the following agents:

1. Paclitaxel Injection

2. Albumin-bound paclitaxel Injection (Abraxane® equivalent formulation)

3. Cisplatin Injection

4. Carboplatin Injection

5. Nivolumab

6. Pembrolizumab

7. Toripalimab

8. Tirilibumab

9. Camrelizumab The specific agent(s) and their combination will be selected based on the patient's clinical treatment protocol. The final regimen must be approved jointly by the principal investigator and the attending physician according to established clinical guidelines and individualized patient factors.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed esophageal squamous cell carcinoma via endoscopic biopsy.
• Primary tumor located in the thoracic esophagus (upper third: ≤25 cm from incisors; middle third: 25-30 cm; lower third: ≥30 cm).
• Clinical staging indicates resectable ESCC based on chest/abdominal enhanced CT, neck lymph node ultrasound, PET-CT/EUS: AJCC/UICC 8th Edition clinical stage excluding T4b, ≥6 lymph node metastases, ≥3 regional lymph node stations involved/metastatic disease (M1).
• Age: 18-75 years inclusive.
• ECOG performance status score of 0 or 1, with life expectancy ≥12 months.
• Adequate organ function: WBC >4.0×10⁹/L, ANC ≥2.0×10⁹/L, platelets >100×10⁹/L, hemoglobin >90g/L; FEV1 ≥1.2L/FVC≥50%/DLCO≥50%; serum bilirubin ≤1.5×ULN; ALT/AST ≤1.5×ULN; SCr ≤120 µmol/L/Ccr ≥60 ml/min.
• Willingness and ability to provide informed consent, comply with follow-up requirements, and participate actively in drug sensitivity testing using PDO models.

Exclusion Criteria

• Clinical staging indicates unresectable ESCC: AJCC/UICC stage T4b disease deemed inoperable by two senior thoracic surgeons; ≥6 lymph node metastases estimated clinically/regionally involving ≥3 stations with lymphadenopathy/metastasis detected via imaging (CT/PET/EUS).
• Currently receiving/was previously treated with chemotherapy/targeted therapy/radiation/or immunotherapy.
• Histopathologic diagnosis other than ESCC confirmed via biopsy (e.g., adenocarcinoma).
• History of prior malignancies except for cured cervical intraepithelial neoplasia or basal cell carcinoma limited locally.
• Autoimmune disease history; ongoing/recurrent corticosteroid/immunosuppressant use.
• Prior immunotherapy treatment; known allergy to investigational drugs; HIV/HBV(HBeAg)/HCV positivity (serum markers).
• Active interstitial lung disease/bronchiectasis; uncontrolled hypertension (SBP≥160 mmHg or DBP≥100 mmHg); cardiovascular disorders (e.g., active ischemia, arrhythmias requiring treatment).
• Pregnancy/lactation; unwillingness to use contraception during study period.
• Non-compliance with protocol requirements, psychiatric comorbidities affecting consent capacity, or concurrent participation in other clinical trials.
• Organ transplantation history (autologous bone marrow/stem cell transplant excluded).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Accurate International Biotechnology (Guangzhou) Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tan Lijie

Chief Physician, Department of Thoracic Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Ethics Review Committee of Zhongshan Hospital, Fudan Univ.

Role: primary

ec@zs-hospital.sh.cn

8602131587871

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

B2024-594R

Identifier Type: -

Identifier Source: org_study_id