Different Radiation Dose With Concurrent Chemotherapy for Thoracic Esophageal Carcinoma

A Multicenter, Prospective, Randomized, Phase III Trial Evaluating High-dose Versus Standard-dose Radiation With Concurrent Chemotherapy for Thoracic Esophageal Squamous Cell Carcinoma

Definitive chemoradiation is the standard treatment for locally advanced esophageal cancer. NCCN (National Comprehensive Cancer Network) recommends radiation dose of 50-50.4 Gy as the definitive radiation dose for esophageal cancer with definitive chemo-radiation. However, as many studies in China showed that the most common recurrence site after definitive chemo-radiation was within the radiation region. But there have not been large randomized clinical trials to investigate the optimal radiation dose with concurrent chemotherapy for esophageal cancer in China. The purpose of this clinical trial is to investigate the optimal radiation dose for thoracic esophageal squamous cell cancer with definitive concurrent chemoradiotherapy.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Radiation: High-dose; Radiation: Standard-dose

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if high-dose radiation with concurrent chemotherapy increases overall survival for thoracic esophageal squamous cell carcinoma

SECONDARY OBJECTIVES:

I. To evaluate if high-dose radiation with concurrent chemotherapy increased progression-free survival for thoracic esophageal squamous cell carcinoma II.To evaluate if high-dose radiation with concurrent chemotherapy increased local control for thoracic esophageal squamous cell carcinoma

OUTLINE:

Patients are randomized to one of the two treatment arms

ARM 1:Patients receive high-dose radiation with concurrent chemotherapy.High-dose RT:59.4 Gy in 33 fractions, 1.8 Gy per fraction, 5days/week.concurrent chemotherapy: Paclitaxel 50mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles.

ARM 2:Patients receive standard-dose radiation with concurrent chemotherapy.Standard-dose RT:59.4 Gy in 33 fractions, 1.8 Gy per fraction, 5days/week . Concurrent chemotherapy: Paclitaxel 50 mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles.

After completion of study therapy, patients are followed up every 3-4 months for 2 years, then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed informed consent form
2. Age: 18-75 years
3. Histological or cytologic diagnosis of esophageal squamous cell carcinoma within one month. Clinical stage T1-4 N0-1 M0-1a (AJCC 6th edition）. Supraclavicular lymphatic metastasis or abdominal lymph node metastasis for mid-thoracic also can be included
4. Karnofsky performance status scores: ≥70
5. Without any prior anticancer therapy
6. BMI≥18kg/m2 or weight loss ≤5% within 3 months
7. Adequate marrow function (within 7 days): White blood cell ≥ 3×109/L,Neutrophils (ANC) ≥1.5×109/L, Platelet count ≥100×109/L, Hemoglobin ≥90g/L. Normal hepatic and renal function (within 14 days): Total bilirubin <1.5 x upper limit of normal (ULN), Alanine aminopeptidase and Aspartase aminotransferase ≤ 2.5 x ULN, creatinine ≤ 1.5xULN
8. Normal cardiac and pulmonary function: Forced expiratory volume at one second (FEV1) ≥1.0 L or FEV1/FVC ≥ 50% pre FEV1; No myocardial infarction within 1 year; no symptomatic heart disease, including myocardial ischemia, congestive heart failure or uncontrolled arrhythmias, roughly normal electrocardiogram; LVEF ≥ 50%，or can receive chemoradiotherapy assessed by cardiologists

Exclusion Criteria:

1. Other or mixed pathological type
2. The second primary tumor of esophageal cancer located outside the radiation area
3. Biopsy-proven invasion of the tracheobronchial tree or tracheoesophageal fistula
4. Mid-thoracic esophageal cancer with supraclavicular lymphatic metastasis and abdominal lymph node metastasis; other metastasis
5. Within 2cm of the gastroesophageal junction
6. Prior chemotherapy, prior thoracic radiation, surgical resection or target therapy of the primary tumor
7. Significant medical or psychiatric illnesses that in the physician's judgment (uncontrolled coronary heart disease, cardiomyopathy and/or heart failure requiring hospitalization. Uncontrolled hypertension or history of myocardial infarction within one year. Uncontrolled diabetes mellitus. Acute bacterial or fungal infection requiring intravenous antibiotics. Acute exacerbation of chronic obstructive pulmonary disease (COPD) or other pulmonary disease requiring hospitalization influencing tumor treatment
8. Refused to sign informed consent form
9. Concurrent pregnancy or lactation
10. History of a second malignancy other than nonmelanoma skin cancer, and cervical cancer in situ.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose; concurrent chemoradiotherapy High-dose RT:59.4 Gy in 33 fractions, 1.8 Gy per fraction, 5days/week; CT: Paclitaxel 50 mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles.	Radiation: High-dose; Drug: concurrent chemotherapy with radiation paclitaxel plus carboplatin are used weekly in both arms
Active Comparator: Standard-dose; concurrent chemoradiotherapy Standard-dose RT:50.4 Gy in 28 fractions, 1.8Gy per fraction, 5days/week; CT: Paclitaxel 50 mg/m2 D1+carboplatin AUC (area under curve) =2 D1, weekly for 6 weeks. After that, patients receive consolidative platinum-based 3-week chemotherapy for 2 cycles.	Radiation: Standard-dose; Drug: concurrent chemotherapy with radiation paclitaxel plus carboplatin are used weekly in both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	5 years

Other Outcome Measures

Outcome Measure	Time Frame
local control rate, recurrence pattern	5 years

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Anhui Shi, MD., Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimated): August 1, 2016

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Esophageal cancer, radiation, chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: ESR-15-11224

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No