Neoadjuvant CRT Combined With Camrelizumab and Nimotuzumab for Initially Inoperable Patients With Esophageal Carcinoma

Neoadjuvant Chemoradiotherapy Combined With Camrelizumab and Nimotuzumab for Initially Inoperable Patients With Locally Advanced Esophageal Squamous Cell Carcinoma: A Prospective, One-arm, Phase II Study (NCRCN)

Neoadjuvant chemoradiotherapy followed by surgery has been the standard modality for locally advance esophageal carcinoma. According to CROSS study, the pathological complete remission rate achieved by paclitaxel and carboplatin with 41.4 Gy/23f was 49% for esophageal squamous cell carcinoma. But the 10-year overall survival rate was only 38%. How to increase the overall survival of esophageal carcinoma is a pivotal task. Both of Camrelizumab and Nimotuzumab have been demonstrated to be efficacious in the neoadjuvant treatment for esophageal squamous cell carcinoma in some small sample-size trials. Therefore, this trial is designed to combine adjuvant chemoradiotherapy with Camrelizumab and Nimotuzumab for resectable & potentially resectable locally advanced esophageal squamous cell carcinoma and explore the safety and primary efficacy of such combination.

Study Overview

• Status: Completed
• Conditions: Toxicity, Drug
• Intervention / Treatment: Drug: neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery

Detailed Description

Trial Title Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab for initially inoperable patients with locally advanced esophageal squamous cell carcinoma: A Prospective, One-arm, Phase II study (NCRCN) Trial Objective To explore the safety and primary efficacy of neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab for initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

Trial Design: To enroll 35 patients with initially inoperable patients with locally advanced esophageal squamous cell carcinoma to receive neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery.

Staging Examination before Adjuvant Treatment: a. ECOG scoring. b. PET-CT, Upper GI endoscopy & endoscopic ultrasound and barium swallow (preferred), or chest contrast CT, abdominal ultrasonography, bone scan, Upper GI endoscopy & endoscopic ultrasound and barium swallow. c. Bronchoscopy for patients with suspicious invasion into trachea or bronchus. d. Pulmonary function test.

Adjuvant chemoradiotherapy Radiotherapy CT Simulation: CT with intravenous contrast is recommended for simulation. Scan thickness should be less than 5 mm from lower margin of mandibular to lower margin of L2. Thermal mask is recommended.

Delineation of Targets: Involved field irradiation is the general principle. Gross Tumor Volume (GTV) is the primary esophageal tumor and the metastatic lymph node. The Clinical Target Volume (CTV) provided a proximal and distal margin of 3 cm and a 0.8 cm radial margin around the primary esophageal tumor and a proximal and distal margin of 1 cm and a 0.8 cm radial margin around the metastatic lymph nodes. The Planning Target Volume (PTV) was defined as an 8-mm margin of the CTV for tumor motion and set-up variations.

Prescription Dose: 41.4 Gy/23f to PTV. Dosimetric Limitation of Organ at Risk: 95% prescription dose should cover 100% PTV and 95% PTV should receive 100% prescription dose. Total Lung: V20<25%, Dmean<13Gy, V5<50%. Spinal Cord: Dmax<45Gy. Heart: V30<40%, Dmean<25Gy.

Treatment Implementation: Radiotherapy is implemented every day. Cone-beam CT should utilized every week to minimize set-up error.

Chemotherapy nab-paclitaxel 50mg/m2+Carboplatin AUC=2 qw×5c, Nimotuzumab 200mg q3w×2c, Camrelizumab 200mg q3w×2c.

Restaging Examination before Surgery: a. ECOG scoring. b. PET-CT and barium swallow (preferred), or chest contrast CT, abdominal ultrasonography, bone scan and barium swallow. c. Pulmonary function test.

Restaging is aiming to exclude patients with disease progression after neoadjuvant treatment.

Surgery Surgery is scheduled for 4 to 6 weeks after completion of adjuvant treatment. McKeown or Ivor-Lewis esophagectomy, including two-field lymphadenectomy with total mediastinal lymph node dissection, is performed. The dissection of left and right recurrent laryngeal nerve nodes is mandatory.

Follow-up: Patients should be follow-up every three months right after the completion of surgery to 2 years after surgery. Then follow-up every half year is allowed to 5 years after surgery. After 5 years, follow-up every year is appropriate. In follow-up, chest contrast CT and abdominal ultrasonography should be implemented. Endoscopy should be undertaken every year for all patients.

Primary Endpoint: 1-year progression free survival (PFS) rate. Secondary Endpoint: Pathological complete remission rate and major pathological remission rate (CAP Cancer Protocol for Esophageal Carcinoma). Surgical conversion rate, Rate of adverse events (CTCAE V4.0), 2-year progression free survival (PFS) rate.1-year, 2-year overall survival rates (OS) .

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provicial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-75 years old;
• Eastern Cooperative Oncology Group (ECOG) 0-1;
• Esophageal squamous cell carcinoma;
• cT2-4aN0-3M0-1a (AJCC 8th) confirmed by radiological examination;
• Initially inoperable at initial diagnosis confirmed by thoracic surgeons;
• No esophageal hemorrhage and no esophageal fistula at initial diagnosis;
• Treatment naive;
• No contraindications for adjuvant chemoradiotherapy, camrelizumab and nimotuzumab;
• Signature of inform consent.

Exclusion Criteria:

• younger than 18 years old or older than 75 years old;
• ECOG>1;
• Esophageal adenocarcinoma, small-cell cancer and other pathological types;
• Presence of esophageal hemorrhage and esophageal fistula at initial diagnosis;
• Previous treatment of chemotherapy, radiotherapy, immune therapy and other treatment;
• Contraindications for chemoradiotherapy, camrelizumab and nimotuzumab;
• No signature of inform consent.

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: Neoadjuvant treatment; Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab	Drug: neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery; neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year progression free survival (PFS) rate	1-year progression free survival (PFS) rate	0 month post neoadjuvant treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of adverse events	Rate of adverse events (CTCAE V4.0)	1 to 2years
Pathological complete remission rate	Pathological complete remission rate (CAP Cancer Protocol for Esophageal Carcinoma)	0 month post surgery
1-, 2-year overall survival rate .	1-, 2-year overall survival rate .	1 to 2years
Major pathological remission rate	Major pathological remission rate (CAP Cancer Protocol for Esophageal Carcinoma)	0 month post surgery
surgical conversion rate	surgical conversion rate	0 month post neoadjuvant

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: April 16, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 28, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Esophageal squamous cell carcinoma; neoadjuvant chemoradiotherapy; camrelizumab; nimotuzumab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Chemically-Induced Disorders; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Drug-Related Side Effects and Adverse Reactions; Antineoplastic Agents, Immunological; Antineoplastic Agents; Nimotuzumab
• Other Study ID Numbers: 2021-ky238

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