Clinical trial NCT05355168: Neoadjuvant CRT Combined With Camrelizumab and Nimotuzumab for Initially Inoperable Patients With Esophageal Carcinoma
Official 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Toxicity, Drug
Keywords: Esophageal squamous cell carcinoma
neoadjuvant chemoradiotherapy
nimotuzumab
camrelizumab
Lead sponsor: Anhui Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2022-05-02
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: To enroll 35 initially inoperable patients with locally advanced esophageal squamous cell carcinoma to receive neoadjuvant chemoradiotherapy combined with Camrelizumab and Nimotuzumab followed by surgery.
Primary purpose: TREATMENT

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.

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) .

Eligibility criteria: 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.

Primary outcomes:
measure: 1-year progression free survival (PFS) rate
timeFrame: 0 month post neoadjuvant treatment
Secondary outcomes:
measure: Rate of adverse events
timeFrame: 1 to 2years
measure: Pathological complete remission rate
timeFrame: 0 month post surgery
measure: 1-, 2-year overall survival rate .
timeFrame: 1 to 2years
measure: Major pathological remission rate
timeFrame: 0 month post surgery
measure: surgical conversion rate
timeFrame: 0 month post neoadjuvant
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provicial Hospital
state: Anhui
Study officials:
References: