Neoadjuvant Chemoradiotherapy Followed by Sequential Immunotherapy for Thoracic Esophageal Squamous Cell Carcinoma (CRIS)

The purpose of study is to investigate the safety and efficacy of sequential immunotherapy with neoadjuvant chemoradiotherapy for esophageal cancer

Study Overview

• Status: Enrolling by invitation
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: paclitaxel; Drug: carboplatin; Drug: tislelizumab; Radiation: radiotherapy

Detailed Description

This is a single-arm, phase Ib study. Eligibility criteria include histologically confirmed ESCC and clinical T3-4aN0M0 or T2-4aN+M0 (AJCC/UICC 8). Patients received neoadjuvant radiotherapy (41.4Gy in 23 fractions) with concurrent chemotherapy (paclitaxel, 50 mg/m2, carboplatin area under the curve of 2mg/mL/min, QW*5). Then followed by two cycles of tislelizumab (200mg, Q3W). The primary endpoint was the pathological complete response (pCR) rate and safety.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 18-75.
• Histology confirmed thoracic esophageal squamous cell carcinoma.
• ECOG ps 0 to 1.
• Resectable or potentially resectable T2-4aN0 or T1-4aN+ patients (AJCC/UICC Clinical Staging of Esophageal squamous cell Carcinoma, 8th edition (cTMN)).
• Length of esophageal lesions <8cm.
• There were no surgical contraindications.
• Neutrophil count ≥1.5*109/L, platelet count ≥10.0*109/L, hemochrome ≥9g/dL; Serum creatinine ≤1.5 times the upper limit of normal value; Bilirubin ≤1.5 times the upper limit of normal value, AST, ALT, AKP≤2.5 times the upper limit of normal value.
• BMI acuity 18.5 kg/m2.
• Informed notification and signed informed consent.

Exclusion Criteria:

• Cervical esophageal cancer (upper part of the lesion in the cervical esophagus). Multifocal esophageal carcinoma, lesion length >8cm.
• Trachea and aorta were invaded (Annex 5).
• Hoarseness caused by the tumor.
• Esophageal fistula.
• Lymph node metastasis in the neck and periceliac artery (AJCC/UICC 8th edition esophageal/esophagogastric junction region lymph node division 1 and 20).
• A history of active autoimmune disorders or syndromes requiring treatment with systemic steroids or immunosuppressants (except for vitiligo or cured childhood asthma/allergies who do not require any intervention in adulthood; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone).
• She is on hormonal or immunosuppressive therapy.
• He's had an organ transplant.
• HIV infection, hepatitis C (hepatitis C antibody positive with HCV-RNA above the detection limit of the assay), chronic active hepatitis B (HBV DNA≥2×103IU/ml or >1×104copies/mL).
• Active tuberculosis, interstitial pneumonia, active infection, poorly controlled diabetes, symptomatic arrhythmia, symptomatic new dysfunction, myocardial infarction, active peptic ulcer, chronic active enteritis within 6 months; Affected during pregnancy or lactation.
• Major surgery in the last three months.
• Severe diabetes mellitus with poor drug control, symptomatic arrhythmia, symptomatic cardiac insufficiency, myocardial infarction within 6 months, chronic active enteritis, chronic nephritis. QTc acuity 470 ms.
• He had a history of malignancy. Previously received chemotherapy, radiotherapy, targeted therapy, immunotherapy and other antitumor therapies.
• Patients with allergic or contraindicated taxa.
• Live vaccine is administered within 30 days before the first dose of immunotherapy.
• Refusal or inability to sign up for ICF study.
• The investigator decided that the patient was not suitable to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IO; chemoradiotherapy sequential tislelizumab	Drug: paclitaxel; paclitaxel, 50 mg/m2, QW*5; Drug: carboplatin; area under the curve of2mg/mL/min, QW*5; Drug: tislelizumab; 200mg Q3W, 2cycles; Radiation: radiotherapy; 41.4Gy in 23 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete pathological response rate	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
R0 resection rate	1 year
Safety will be analyzed through the incidence of adverse events, serious adverse events	Up to 28 days from last dose
2-year overall survival rate	2 years
2-year Disease-free survival rate	2 years

Collaborators and Investigators

• Sponsor: Qiu Guoqin

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant; tislelizumab; chemoradiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Carboplatin; Paclitaxel; Tislelizumab
• Other Study ID Numbers: IRB- 2022-213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No