Neoadjuvant Chemoradiotherapy Combined With Camrelizumab and Nimotuzumab for Esophageal Squamous Cell Carcinoma

Sponsor

Anhui Provincial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05355168

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Toxicity, Drug	Procedure: neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery	Phase 1/Phase 2

Detailed Description

Trial Title Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab for resectable & potentially resectable locally advanced esophageal squamous cell carcinoma: A phase I/II study (NCRCN) Trial Objective To explore the safety and primary efficacy of neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab for resectable & potentially resectable locally advanced esophageal squamous cell carcinoma.

Trial Design: To enroll 57 patients with resectable & potentially resectable 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 Paclitaxel 50mg/m2+Carboplatin AUC=2 qw×5c, Nimotuzumab 200mg qw×5c, Camrelizumab 200mg q4w×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.

Pulmonary function test.

Restaging is aiming to exclude patients with disease progression after adjuvant 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 3 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: Pathological complete remission rate and major pathological remission rate (CAP Cancer Protocol for Esophageal Carcinoma).

Secondary Endpoint: Rate of adverse events (CTCAE V4.0), Complete resection rate, 1-, 2-, 3-year Disease-free survival rate (DFS).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

57 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

To enroll 57 patients with resectable & potentially resectable locally advanced esophageal squamous cell carcinoma to receive neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery.To enroll 57 patients with resectable & potentially resectable locally advanced esophageal squamous cell carcinoma to receive neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Chemoradiotherapy Combined With Camrelizumab and Nimotuzumab for Resectable & Potentially Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase I/II Study (NCRCN)

Actual Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant treatment Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab	Procedure: neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery

Arm

Intervention/Treatment

Experimental: Neoadjuvant treatment

Neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab

Procedure: neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery

neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery

Outcome Measures

Primary Outcome Measures

Pathological complete remission rate [1 month post adjuvant treatment]
Pathological complete remission rate (CAP Cancer Protocol for Esophageal Carcinoma)
Major pathological remission rate [1 month post adjuvant treatment]
Major pathological remission rate (CAP Cancer Protocol for Esophageal Carcinoma)

Secondary Outcome Measures

Rate of adverse events [1 to 3 years]
Rate of adverse events (CTCAE V4.0)
Complete resection rate [1 month post adjuvant treatment]
Complete resection rate
1-, 2-, 3-year Disease-free survival rate (DFS). [1 to 3 years]
1-, 2-, 3-year Disease-free survival rate (DFS).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18-75 years old;
Eastern Cooperative Oncology Group (ECOG) 0-1;
Esophageal squamous cell carcinoma;
cT2-4aN0-3M0 (AJCC 8th) confirmed by radiological examination;
Resectable and potentially resectable 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 70 years old;
ECOG>1;
Esophageal adenocarcinoma, small-cell cancer and other pathological types;
cT1anyNM0, cT4banyNM0, c anyTanyNM0 confirmed by radiological examination;
Unresectable at initial diagnosis confirmed by thoracic surgeons;
Presence of esophageal hemorrhage and esophageal fistula at initial diagnosis;
Previous treatment of chemotherapy, radiotherapy, immune therapy and other treatment;
Contraindications for adjuvant chemoradiotherapy, camrelizumab and nimotuzumab;
Disease progression after adjuvant treatment. j. No signature of inform consent.