Efficacy and Safety of Cadonilimab and Chemoradiotherapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

NCT06715501 | Enrolling By Invitation DMC

• 1 other identifier: AK104-IIT-C-E-0195
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single center, prospective, single arm exploratory clinical trial aimed at evaluating the efficacy and safety of sequential chemoradiotherapy combined with cetuximab in unresectable locally advanced esophageal squamous cell carcinoma. Patients with advanced unresectable esophageal squamous cell carcinoma who meet the criteria, after signing the informed consent form, will first receive induction therapy with cetuximab combined with paclitaxel and carboplatin chemotherapy for 2 cycles. Within 3 weeks after the second dose, RECIST v1.1 will be used for clinical tumor imaging evaluation, and if necessary, gastroscopy biopsy will be performed. Patients without progression will further receive synchronous radiotherapy and chemotherapy. PTV-C accepts 50.4Gy, 28 times; Radiotherapy combined with paclitaxel and carboplatin weekly regimen. Within three months after completion, conduct safety assessments and preliminary evaluations of tumor response every three weeks. Consolidate treatment with cetuximab until 1 year or intolerance or disease progression occurs.

Conditions

Locally Advanced Esophageal Squamous Cell Carcinoma; II-IIIB Stages

Keywords

locally advanced ESCC; II-IIIB stage; Cadonilimab; Chemoradiotherapy

Outcome Measures

Primary Outcomes (2)

• 2-year progression free survival rate

  2 year after the end of treatment

• Incidence of Treatment-Emergent Adverse Events

  The incidence of adverse events (AE) and serious adverse events (SAE) within three months after radiotherapy, and the incidence of treatment termination caused by AE/SAE

  Within three months after radiotherapy

Secondary Outcomes (2)

• Progression free survival (PFS)

  From the randomization date until the first recorded date of progression or death from any cause, whichever comes first, assessed up to 36 months

• Overall survival (OS)

  From the randomization date until death from any cause，assessed up to 36 months

Study Arms (1)

Cadonilimab combined with Chemoradiotherapy

EXPERIMENTAL

Patients with advanced unresectable esophageal squamous cell carcinoma who meet the criteria, will first receive induction therapy with cetuximab combined with paclitaxel and carboplatin chemotherapy for 2 cycles. Within 3 weeks after the second dose, RECIST v1.1 will be used for clinical tumor imaging evaluation. Patients without progression will further receive synchronous radiotherapy and chemotherapy. PTV-C accepts 50.4Gy, 28 times; Radiotherapy combined with paclitaxel and carboplatin weekly regimen. Within three months after completion, conduct safety assessments and preliminary evaluations of tumor response every three weeks. Consolidate treatment with cetuximab until 1 year or intolerance or disease progression occurs.

Drug: Cadonilimab; Radiation: radiotherapy; Drug: carboplatin, paclitaxel

Interventions

Cadonilimab DRUG

Cadonilimab is a PD-1/CTLA-4 bispecific antibody. The drug is administered at a fixed dose of 10mg/kg, intravenously (i.v.), on day 1, every 3 weeks (q3w), until disease progression or intolerable toxicity occurs, with a maximum treatment duration of 1 year.

Cadonilimab combined with Chemoradiotherapy

radiotherapy RADIATION

GTV is defined as visible lesions (GTVp: primary lesion; GTVn: metastatic lymph nodes), CTVp is defined as 3cm above and below the primary lesion, with 0.5cm outward expansion around the periphery, and CTVn is defined as 0.5cm outward expansion of GTVn; PTVp is an outward expansion of 0.5cm for CTVp, and PTVn is an outward expansion of 0.5cm for CTVn. Radiotherapy dose: DT50.4Gy/28f, once daily, 5 times a week

Cadonilimab combined with Chemoradiotherapy

carboplatin, paclitaxel DRUG

Induction chemotherapy: carboplatin 5AUC，q3w; Paclitaxel 135mg/m2,q3w. Simultaneous chemotherapy: 2AUC/W，total 5w; Paclitaxel 50mg/m2/w，total 5w

Cadonilimab combined with Chemoradiotherapy

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of locally advanced esophageal squamous cell carcinoma (TN+M0 or T2-3NxM0) by histological examination and/or cytological examination；
• TNM clinical stage II-IIIB that cannot be surgically resected ;
• ECOG score 0-1 points;
• Expected survival ≥ 6 months;
• Without anti-tumor treatment in the past (including but not limited to surgery, radiotherapy, chemotherapy, anti vascular therapy, immunotherapy, etc.);
• Pathological specimens available;
• At least one measurable target lesion or pathological enlargement of lymph nodes with a single lymph node CT scan short diameter ≥ 15mm (according to the efficacy evaluation criteria for solid tumors RECIST 1.1) ;
• The main organ functions well and meets the following standards:
• Blood routine examination (without blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days): hemoglobin (Hb) ≥ 90 g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 80 × 109/L;
• Biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum total bilirubin (TBIL) ≤ 1.5 × ULN (Gilbert syndrome subjects, ≤ 3 × ULN); Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance rate ≥ 60mL/min;
• Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
• Subjects with fertility must use appropriate contraception methods during the study period and within 120 days after the last dose. They must have a negative serum pregnancy test within 7 days before enrollment and must be non lactating subjects.

You may not qualify if:

• Other malignant tumors within 5 years prior to the start of this study;
• High risk of gastrointestinal bleeding, esophageal fistula or perforation;
• Unrelieved toxic reactions of grade ≥ 1(excluding alopecia and fatigue; hematological toxicity must be recovered to grade ≤1 or baseline before enrollment);
• Weight loss of ≥20% within 90 days prior to signing the informed consent form;
• Poor nutritional status or a PG-SGA score of ≥9;
• Any severe and/or uncontrolled diseases. This includes:
• Uncontrolled blood pressure (systolic pressure ≥150mmHg or diastolic pressure ≥100mmHg);
• Suffering from grade ≥2 myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥470ms), and grade ≥2 congestive heart failure (New York Heart Association \[NYHA\] classification);
• History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute pulmonary diseases;
• Active or uncontrolled severe infections (grade ≥2 CTCAE infections);
• Liver cirrhosis, active hepatitis; active hepatitis (for hepatitis B: positive HBsAg and HBV DNA levels exceeding the upper limit of normal; for hepatitis C: positive HCV antibodies and HCV viral load exceeding the upper limit of normal);
• Active syphilis;
• Renal failure requiring hemodialysis or peritoneal dialysis;
• A history of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• Poorly controlled diabetes (fasting blood glucose \[FBG\] \> 10mmol/L);

Sponsors & Collaborators

• First Affiliated Hospital of Ningbo University: lead

Study Sites (1)

First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, 315001, China

Location

MeSH Terms

Interventions

Radiotherapy; CP protocol

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: December 4, 2024
• Study Start: December 1, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

CN (1)