NCT07757022

Brief Summary

This study aims to integrate multi-omics data (genomics, transcriptomics, proteomics) from esophageal cancer patients with artificial intelligence and digital twin technology to construct personalized virtual patient models that precisely simulate individual responses to targeted therapies. Through a drug simulation platform, this study will rapidly screen potential effective drug combinations and optimize dosage and treatment regimens. The project attempts to replace portions of traditional clinical trials with virtual clinical trial technology, substantially shortening the R\&D cycle, reducing costs, and effectively addressing the complexity of individualized treatment. Specifically, this study will conduct a head-to-head virtual clinical trial parallel to a real-world investigator-initiated trial (IIT) in patients with locally advanced esophageal squamous cell carcinoma, comparing the efficacy predictions from the virtual model with actual clinical outcomes. The ultimate goal is to explore the application of large-scale AI models in esophageal cancer targeted therapy, provide personalized treatment recommendations, and advance the implementation of precision medicine in esophageal cancer.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P75+ for all trials

Timeline
29mo left

Started Jul 2026

Typical duration for all trials

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress2%
Jul 2026Dec 2028

First Submitted

Initial submission to the registry

July 30, 2026

Completed
Same day until next milestone

Study Start

First participant enrolled

July 30, 2026

Completed
12 days until next milestone

First Posted

Study publicly available on registry

August 11, 2026

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

August 11, 2026

Status Verified

July 1, 2026

Enrollment Period

1.3 years

First QC Date

July 30, 2026

Last Update Submit

August 10, 2026

Conditions

Keywords

Esophageal CancerComputational MedicineMulti-OmicsArtificial IntelligenceVirtual Clinical TrialsDigital TwinToripalimab

Outcome Measures

Primary Outcomes (1)

  • Event-Free Survival (EFS)

    Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: inoperability due to any cause, distant metastasis, local recurrence, or death from any cause, whichever occurs first. Distant metastasis is confirmed by: (1) pathological confirmation of squamous cell carcinoma metastasis in other organs, soft tissues, or skin; (2) PET-CT revealing non-local recurrent hypermetabolic soft tissue lesions; or (3) CT, MRI, or abdominal ultrasound diagnosis of distant metastasis.

    From randomization up to 36 months

Secondary Outcomes (9)

  • Pathological Complete Response (pCR) Rate

    At the time of surgery (approximately 4-8 weeks after completion of neoadjuvant therapy)

  • Overall Survival (OS)

    From randomization up to 36 months

  • Disease-Free Survival (DFS)

    From surgery up to 36 months

  • Objective Response Rate (ORR)

    Up to 24 months

  • R0 Resection Rate

    At the time of surgery (approximately 4-8 weeks after completion of neoadjuvant therapy)

  • +4 more secondary outcomes

Study Arms (2)

Neoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance

Patients in this group receive neoadjuvant immunochemotherapy consisting of toripalimab (JS001) 240 mg intravenously on day 3, paclitaxel 175 mg/m² intravenously on day 1, and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. Following surgery (within 3 weeks ± 3 days, no later than 2.5 months postoperatively), patients receive postoperative toripalimab maintenance therapy at 240 mg intravenously every 3 weeks for up to 8 cycles (approximately 6 months) or until disease progression, unacceptable toxicity, or withdrawal of consent.

Drug: ToripalimabDrug: PaclitaxelDrug: Cisplatin

Neoadjuvant Chemotherapy plus Surgery

Patients in this group receive neoadjuvant chemotherapy consisting of paclitaxel 175 mg/m² intravenously on day 1 and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. No postoperative maintenance therapy is administered. Patients are followed up according to the same schedule as the experimental group.

Drug: PaclitaxelDrug: Cisplatin

Interventions

Recombinant humanized anti-PD-1 monoclonal antibody administered at 240 mg IV on day 3 of each 21-day cycle for 2 cycles preoperatively, followed by 240 mg IV Q3W postoperatively for up to 8 cycles.

Also known as: JS001
Neoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance

Administered at 175 mg/m2 IV on day 1 of each 21-day cycle for 2 cycles preoperatively.

Also known as: PTX
Neoadjuvant Chemotherapy plus SurgeryNeoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance

Administered at 75 mg/m2 IV on day 1 of each 21-day cycle for 2 cycles preoperatively.

Also known as: DDP
Neoadjuvant Chemotherapy plus SurgeryNeoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

The study population consists of patients with locally advanced thoracic esophageal squamous cell carcinoma, clinical stage T1N1-3M0 or T2-3N0-3M0 (8th UICC-TNM staging), aged 18 to 75 years, with ECOG performance status 0-1, no prior antitumor therapy for esophageal cancer, expected to achieve R0 resection, and adequate bone marrow, liver, and renal function meeting the inclusion criteria. Eligible patients will be consecutively enrolled at Henan Cancer Hospital.

You may qualify if:

  • Treatment-naïve patients with clinical stage locally advanced (T1N1-3M0 or T2-3N0-3M0) thoracic esophageal squamous cell carcinoma, according to the 8th UICC-TNM staging system.
  • Cervical color Doppler ultrasound shows no suspicious metastatic lymph nodes, or patients with suspected lymph node metastasis on ultrasound who are eligible for three-field lymphadenectomy.
  • No prior antitumor therapy for esophageal cancer (including chemotherapy, radiotherapy, or immunotherapy).
  • Preoperative evaluation of organ function indicates no surgical contraindications.
  • Adequate bone marrow, liver, and renal function, confirmed by the following laboratory tests performed within 7 days prior to enrollment:
  • Hemoglobin ≥ 90 g/L;
  • White blood cell count ≥ 4.0 × 10\^9/L;
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
  • Platelet count ≥ 100 × 10\^9/L;
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
  • ALT and AST ≤ 2.5 × ULN;
  • International normalized ratio (INR) of prothrombin time ≤ 1.5 × ULN, with activated partial thromboplastin time (APTT) within normal range;
  • Serum creatinine ≤ 1.5 × ULN.
  • No prior chemotherapy, radiotherapy, or hormone therapy for malignant tumors; no history of other malignancies, except for prostate cancer patients who received hormone therapy and have achieved disease-free survival (DFS) \> 5 years.
  • Expected to achieve R0 resection.
  • +4 more criteria

You may not qualify if:

  • Presence of multiple primary malignancies (synchronous or metachronous).
  • Active infections requiring systemic treatment.
  • Requirement for continuous systemic corticosteroid therapy (\>10 mg/day prednisone or equivalent) for comorbid conditions.
  • Unstable angina within 3 months or myocardial infarction within 6 months prior to enrollment.
  • Psychiatric disorders that may affect study compliance.
  • Known or concurrent hemorrhagic disorders.
  • Female patients who are pregnant or breastfeeding.
  • Patients with pre-existing or concurrent pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, or other severe pulmonary impairment.
  • Autoimmune diseases, immunodeficiency states, or history of organ transplantation.
  • Known hypersensitivity to the study drugs (toripalimab, paclitaxel, cisplatin) or their excipients.
  • Abnormal coagulation function (PT \> 16s, APTT \> 53s, TT \> 21s, Fib \< 1.5 g/L), bleeding tendency, or patients receiving thrombolytic or anticoagulant therapy.
  • Bronchial asthma requiring intermittent use of bronchodilators or medical intervention.
  • Active hepatitis B (HBV) or hepatitis C (HCV) infection. (Patients who are HBsAg positive or HBcAb positive may be eligible if HBV DNA is below the lower limit of detection/quantification; patients who are HCV antibody positive may be eligible if HCV RNA is below the lower limit of detection/quantification.)
  • Human immunodeficiency virus (HIV) positivity.
  • Any other condition that, in the investigator's judgment, may compromise patient safety, interfere with study compliance, or preclude successful completion of the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Biospecimen

Retention: SAMPLES WITH DNA

Both tissue and blood biospecimens are collected. Tissue samples (primary tumor, adjacent tissue within 2 cm, and normal esophagus \>2 cm from tumor) are obtained via pretreatment endoscopic biopsy and during surgery, preserved in cryovials at -80°C and RNA preservation solution. Peripheral blood samples (5 mL EDTA tubes × 2 per timepoint) are collected before neoadjuvant treatment and prior to surgery, centrifuged for serum, plasma, and buffy coat separation, and stored at -80°C. These biospecimens are used for whole-exome sequencing, RNA sequencing, and multi-omics analysis to generate virtual patient models.

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

toripalimabPaclitaxelCisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum Compounds

Central Study Contacts

Yan Zheng, M.D./Ph.D

CONTACT

Song, M.D./Ph.D

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
OTHER
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director

Study Record Dates

First Submitted

July 30, 2026

First Posted

August 11, 2026

Study Start

July 30, 2026

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2028

Last Updated

August 11, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will not share