A Phase II Trial to Compare Efficacy and Safety of CRT VS Neo-CRT in Patients Who Achieved CCR for Esophageal Cancer

Phase 2

• Conditions: Stage III Esophageal Cancer; Stage II Esophageal Cancer
• Interventions: Radiation: Definitive Radiochemotherapy; Procedure: Neoadjuvant Radiochemotherapy

• Registration Number: NCT02959385
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

Neoadjuvant chemoradiotherapy(Neo-CRT) plus surgery has been regarded as a standard of care for patients with resectable locally advanced oesophageal cancer. Many studies suggest that definitive Radiochemotherapy(CRT) has similar efficacy as neoadjuvant chemoradiotherapy plus surgery for esophageal cancers who respond to chemoradiation. Herein, a single center prospective randomized phase II clinical trial will be carried out to compare efficacy and safety of definitive radiochemotherapy versus neoadjuvant radiochemotherapy plus radical resection in patients who achieved clinical complete response(CCR) after neoadjuvant radiochemotherapy for stage II-III 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 achieved clinical complete response 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. Compare the relationship and consistency between pathological complete response of endoscopic biopsy specimens after neoadjuvant treatment and pathological complete response of surgical specimens in neoadjuvant radiochemotherapy plus radical resection group;

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

Clinical Complete Response After Neoadjuvant Treatment: Endoscope biopsy pathologic diagnosis indicate pathologic complete response after Neoadjuvant treatment; upper gastrointestinal/chest CT and symptom assessment indicate clinical complete response after Neoadjuvant treatment (Concurrent Radiochemotherapy: Radiotherapy, Intensity Modulation Radiation Therapy(IMRT), 40Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2), 1st/8th/15th/22nd day

Study Timeline

• Study Start: 2016-09
• Status Verified: 2016-10
• Study First Submitted: 2016-10-29
• Study First Submitted QC: 2016-11-06
• Study First Posted: 2016-11-09
• Last Update Submitted: 2017-07-13
• Last Update Posted: 2017-07-18
• Primary Completion: 2018-09
• Study Completion: 2021-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Thoracic esophageal cancer patients or esophagocardial cancer patients, with locally advanced resectable tumor, clinically identified before treatment as T1-3N+M0 according to UICC(International Union Against Cancer) TNM(primary tumor, regional nodes, metastasis) Classification of Malignant Tumours, 7th ed.
2. Untreated patients who have not received any antitumor therapy
3. Life expectancy >6 months
4. Age: 18-70 years
5. White blood cell count ≥4.0×109/l, ANC(absolute neutrophil count) ≥1.5×109/l, thrombocyte count ≥1011/l, hemoglobin ≥90 g/l; normal liver and kidney functions
6. WHO PS(Performance Status): 0-1
7. 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. Pregnant or lactating women
5. Patients who agree without acknowledgement as a result of psychological, family or social factors
6. Patients with CTCAE(Common Terminology Criteria Adverse Events Version 4.0) grade ≥2 peripheral neuropathy
7. Patients who have ever had malignant tumors other than esophageal cancer
8. Patients with a history of diabetes for >10 years with unsatisfactory control of blood glucose level
9. Patients with serious heart, lung, liver or kidney dysfunction, hematopathy, immune system disease or cachexia who therefore cannot tolerate chemotherapy or surgery
10. Others.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Definitive Radiochemotherapy	Definitive Radiochemotherapy	Concurrent Radiochemotherapy: Radiotherapy,IMRT, 60Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2) 1st/8th/15th/22nd day.
Neoadjuvant Radiochemotherapy	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	Neoadjuvant Radiochemotherapy	Concurrent Radiochemotherapy: Radiotherapy,IMRT, 60Gy; Chemotherapy, Docetaxel （25mg/m2）+Cisplatin (25mg/m2) 1st/8th/15th/22nd day.
Neoadjuvant Radiochemotherapy	Neoadjuvant 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.

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

Secondary Outcome Measures

Name	Time	Method
Comparison between gross tumor volume (GTV) delineated with ultrasonic endoscopically placed titanium clips and GTV with conventional contouring method in thoracic esophageal cancer	1 year	patients undergo titanium clips placement on tumor boundaries under ultrasonic endoscopy before radiotherapy CT simulation. According to the clips, the reference GTVs are contoured by one experienced radiation oncologist. With the help of Eclipse treatment planning system, clips on CT are concealed. Two other radiation oncologists of expertise in oesophageal cancer delineate GTVs, defined as conventional GTVs, on the basis of endoscopy and oesophageal barium radiography. The two sets of GTVs are compared and analysed.
Progression-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.
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.
Comparison of pathological diagnosis between specimens of endoscopic biopsy and surgically resected in esophageal cancer	2 years	In the group of neoadjuvant radiochemotherapy plus surgery, we will compare the pathological diagnosis between specimens of endoscopic biopsy after neoadjuvant treatment and surgically resected.
Determination of internal target volume (ITV) of thoracic esophageal cancer by evaluating movement of ultrasonic endoscopically placed titanium clips, with or without swallowing, during radiotherapy simulation	1 year	after titanium clips placement adjacent to esophageal cancer under ultrasonic endoscopy, clips movements in different borders and different directions are observed during radiotherapy simulation to determine the ITV of esophageal cancer, with or without swallowing.

Trial Locations

Locations (1)

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