Neoadjuvant Immunochemotherapy and Chemoradiotherapy Followed by Surgery for Advanced Esophageal Squamous Cell Carcinoma

NCT06764355 | Recruiting Phase 2 DMC

• 1 other identifier: 202409007MIPE
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Effective systemic therapy such as nivolumab as an adjuvant therapy has been demonstrated to improve the outcomes of patients receiving neoadjuvant chemoradiotherapy (CRT) for locoregional esophageal cancer. A more effective systemic therapy with anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) plus cisplatin-based doublet chemotherapy, which has shown with high tumor response rate and improved survivals in patients with late-stage ESCC, may provide crucial benefit to patients with locally advanced disease by improving the systemic control, downstaging the locoregional tumor burden and reducing recurrence and metastasis. Collectively, the investigators hypothesize that total neoadjuvant therapy (TNT) approach-consisting of induction immunochemotherapy followed by CRT-is a promising strategy to enhance the outcomes for participants with locally advanced esophageal squamous cell carcinoma.

Conditions

Total Neoadjuvant Treatment; Pathological Complete Response; ESCC

Keywords

ESCC

Outcome Measures

Primary Outcomes (1)

• pathological complete response

  To evaluate the pathological complete response (pCR) rate of participants receiving total neoadjuvant therapy with induction immunochemotherapy and chemoradiotherapy (CRT) followed by surgery in operable ESCC.

  through study completion, an average of 6 months

Secondary Outcomes (8)

• Major pathological response

  through study completion, an average of 6 months

• R0 resection rate

  through study completion, an average of 6 months

• Disease-free survival

  from esophagectomy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 50 months

• Event-free survival

  from enrollment to an event which may include radiographic progression, clinical progression, local or distant recurrence, second aerodigestive tract squamous cell carcinoma, and death from any cause, whichever came first, assessed up to 50 months

• Distant metastasis-free survival

  from esophagectomy until evidence of distant metastasis recurrence or death from any cause, whichever came first, assessed up to 50 months

Study Arms (1)

Total Neoadjuvant Therapy

EXPERIMENTAL

"neoadjuvant immunochemotherapy" and "chemoradiotherapy"

Drug: Tislelizumab; Drug: Paclitaxel; Drug: Cisplatin; Radiation: Chemoradiotherapy

Interventions

Tislelizumab DRUG

200 mg, 1h-IVF, Q3W on day 1 for 2 cycles

Total Neoadjuvant Therapy

Paclitaxel DRUG

Paclitaxel 175 mg/m2, 3h-IVF, Q3W on day 1 for 2 cycles

Total Neoadjuvant Therapy

Cisplatin DRUG

Cisplatin 75 mg/m2, 2h-IVF, Q3W on day 1 for 2 cycles

Total Neoadjuvant Therapy

Chemoradiotherapy RADIATION

Chemoradiotherapy * Paclitaxel 50 mg/m2, 1h-IVF, on days 1, 8,15, 22, and 29; * Cisplatin 30 mg/m2,1h-IVF, on days 1, 8,15, 22, and 29; * RT: 1.8 Gy/fraction, 5 days a week, for 25 fractions (total dose= 45 Gy).

Total Neoadjuvant Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically proven squamous cell carcinoma of the intrathoracic esophagus.
• Locally advanced disease, which is defined by the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition), fulfilling one of the following criteria as determined by staging procedures (including but not limited to endoscopic ultrasound, computed tomography, bronchoscopy or positron emission tomography):
• cT3/4a, N0, M0;
• cT1-4a, N1-3, M0.
• Tumor length longitudinal ≤ 10cm and radial ≤ 5cm.
• The tumor must not extend more than 2cm into the stomach.
• No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.
• Age ≥ 18 and ≤ 75 years old.
• Performance status ECOG 0\~1.
• Adequate bone marrow reserves, defined as:
• white blood cells (WBC) ≥ 3,000/µl or neutrophil count (ANC) ≥ 1,500/µl;
• platelets ≥ 100,000/µl.
• Adequate liver function reserves, defined as:
• hepatic transaminases ≤ 2.5 x upper limit of normal (ULN);
• serum total bilirubin ≤ 2.0 x upper limit of normal (ULN).

You may not qualify if:

• Adenocarcinoma
• Previous thoracic irradiation
• Previous systemic chemotherapy
• Has received prior therapy with an anti-PD-1 or anti-PD-L1
• Synchronous diagnosis of squamous cell carcinoma in the aerodigestive tract, other than esophageal cancer.
• Prior malignancy, except for the following:
• adequately treated basal cell or squamous cell skin cancer;
• in-situ cervical cancer;
• a "cured" malignancy more than 5 years prior to enrollment.
• Significant co-morbid disease, which prohibits the conduction of immunochemotherapy, concurrent CRT, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders.
• Documented myocardial infarction within the 6 months preceding registration (pretreatment ECG evidence of infarct only will not exclude patients). Patients with a history of significant ventricular arrhythmia requiring medication. Patients with a history of 2nd or 3rd degree heart block.
• Pre-existing motor or sensory neurotoxicity greater than grade 1.
• Patients with prior allergic reactions to drug containing Cremophor, such as teniposide or cyclosporine.
• Weight loss \> 15%.
• Dementia or altered mental status that would prohibit the understanding and completion of informed consent.

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• BeiGene: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100229, Taiwan

RECRUITING

MeSH Terms

Interventions

tislelizumab; Paclitaxel; Cisplatin; Chemoradiotherapy

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Central Study Contacts

Chih-Hung Hsu, M.D., PhD

CONTACT

+886-2-23123456; chihhunghsu@ntu.edu.tw

Chien-Huai Chuang, M.D.

CONTACT

+886-972652955; chuang.chienhuai@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: January 8, 2025
• Study Start: July 23, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)