Clinical trial NCT02850991: Different Radiation Dose With Concurrent Chemotherapy for Thoracic Esophageal Carcinoma
Official title: A Multicenter, Prospective, Randomized, Phase III Trial Evaluating High-dose Versus Standard-dose Radiation With Concurrent Chemotherapy for Thoracic Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Esophageal Cancer
Keywords: Esophageal cancer, radiation, chemotherapy
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2016-08-01
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: High dose radiation plus chemotherapy of paclitaxel and carboplatin vs standard dose radiation plus chemotherapy of paclitaxel and carboplatin.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: 5 years
Secondary outcomes:
measure: Progression-free survival
timeFrame: 5 years
Other outcomes:
measure: local control rate, recurrence pattern
timeFrame: 5 years
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Anhui Shi, MD.
role: PRINCIPAL_INVESTIGATOR
References: