Efficacy and Safety of Neo-CRT Followed Surgery Compared With Definitive CRT in Patients With Initial Unresectable ESO

Phase 2

• Conditions: Unresectable Esophageal Cancer
• Interventions: Radiation: Definitive Radiochemotherapy; Procedure: Neoadjuvant Radiochemotherapy followed by surgery

• Registration Number: NCT04137679
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

Definitive chemoradiotherapy(CRT) has been regarded as a standard of care for patients with unresectable locally advanced esophageal cancer. Patients who are sensitive to CRT can achieve significantly down staging. Whether this part of patients could benefit from further surgical treatment remains unknown. Herein, a single center prospective randomized phase II clinical trial will be carried out to compare efficacy and safety of definitive CRT versus neo-CRT plus radical resection in patients who achieved down staging after neo-CRT for stage T4NxM0 esophageal Cancer.

Detailed Description

1. Compare progression-free survival (PFS) and overall survival (OS) of definitive radiochemotherapy versus(VS) neoadjuvant radiochemotherapy plus radical resection for esophageal cancer patients who down stage from inoperable to operable after neoadjuvant treatment;

2. Compare the toxic and side effects of definitive radiochemotherapy versus neoadjuvant radiochemotherapy plus radical resection for esophageal cancer patients who achieved clinical complete remission after neoadjuvant treatment;

3. Assess impact of definitive radiochemotherapy versus neoadjuvant radiochemotherapy plus radical resection on quality of life of patients.

Concurrent Radiochemotherapy: Radiotherapy, Intensity Modulation Radiation Therapy(IMRT), 40Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2), 1st/8th/15th/22nd day

Study Timeline

• Status Verified: 2019-08
• Study First Submitted: 2019-10-22
• Study First Submitted QC: 2019-10-22
• Study First Posted: 2019-10-24
• Last Update Submitted: 2019-10-29
• Study Start: 2019-11-01
• Last Update Posted: 2019-11-01
• Primary Completion: 2020-01-01
• Study Completion: 2022-08-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Thoracic esophageal cancer patients or esophagogastric junction cancer patients, with locally advanced unresectable tumor, clinically identified before treatment as T4bNxM0 or lymph node metastases (LNM)invading adjacent structures according to UICC(International Union Against Cancer) TNM(primary tumor, regional nodes, metastasis) Classification of Malignant Tumours, 8th ed.
2. Initial unresectable assessed by surgeon.
3. Patients able to tolerate surgery.
4. Untreated patients who have not received any antitumor therapy.
5. Life expectancy > 6 months.
6. Age: 18-70 years.
7. White blood cell count ≥4.0×10^9/L, ANC(absolute neutrophil count) ≥1.5×10^9/L, thrombocyte count ≥100×10^9/L, hemoglobin ≥90 g/L; normal liver and kidney functions.
8. WHO PS(Performance Status): 0-1.
9. Patients who understood the study and gave signed informed consent.

Exclusion Criteria

1. Patients who have already received antitumor therapy, including chemotherapy, radiotherapy or surgery.
2. Patients with hemorrhage or complicated hemorrhage.
3. Other uncontrollable patients who are not suitable for surgery.
4. Patients who deny to accept surgery.
5. Pregnant or lactating women.
6. Patients who agree without acknowledgement as a result of psychological, family or social factors.
7. Patients with CTCAE(Common Terminology Criteria Adverse Events Version 4.0) grade ≥2 peripheral neuropathy.
8. Patients who have ever had malignant tumors other than esophageal cancer.
9. Patients with a history of diabetes for >10 years with unsatisfactory control of blood glucose level.
10. Patients with serious heart, lung, liver or kidney dysfunction, hematopathy, immune system disease or cachexia who therefore cannot tolerate chemotherapy or surgery.
11. Patients with severe infection.
12. Patients with uncontrolled diabetes, random blood glucose > 200mg/L, fasting glucose >140mg/L.
13. Patients with other severe disease, such as myocardial infarction in the last 6 months.
14. Patients who participate in other clinical trials right now or in the last 4 weeks.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Neoadjuvant Radiochemotherapy followed by surgery	Definitive Radiochemotherapy	Concurrent Radiochemotherapy: Radiotherapy,IMRT, 40Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2) 1st/8th/15th/22nd day; Receive radical surgery 4 to 6 weeks later.
Definitive Radiochemotherapy	Definitive Radiochemotherapy	Concurrent Radiochemotherapy: Radiotherapy,IMRT, 60Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2) 1st/8th/15th/22nd day.
Definitive Radiochemotherapy	Neoadjuvant Radiochemotherapy followed by surgery	Concurrent Radiochemotherapy: Radiotherapy,IMRT, 60Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2) 1st/8th/15th/22nd day.
Neoadjuvant Radiochemotherapy followed by surgery	Neoadjuvant Radiochemotherapy followed by surgery	Concurrent Radiochemotherapy: Radiotherapy,IMRT, 40Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2) 1st/8th/15th/22nd day; Receive radical surgery 4 to 6 weeks later.

Primary Outcome Measures

Name	Time	Method
Overall survival	5 years	Compare overall survival of definitive radiochemotherapy versus neoadjuvant radiochemotherapy plus radical resection for esophageal cancer patients who achieved clinical complete response after neoadjuvant radiochemotherapy
Disease-free survival	3 years	Compare progression-free survival of definitive radiochemotherapy versus neoadjuvant radiochemotherapy plus radical resection for esophageal cancer patients who achieved clinical complete response after neoadjuvant radiochemotherapy.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment	5 years	grade 3 or 4 toxicity of leukocytes, febrile neutropenia, thrombocytes, hemoglobin, nausea/vomiting, diarrhea, stomatitis, esophagitis, cardiovascular.

Trial Locations

Locations (1)

Department of Radiation Oncology, Tianjin Medical University Cancer Hospital; 🇨🇳 Tianjin, Tianjin, China