Dose Escalation by Boosting Radiation Dose Within the Primary Tumor Using 18FDG-PET/CT for Unresectable Thoracic Esophageal Cancer

Study Overview
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Brief Summary
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Most local failures after definitive chemoradiation for unresectable esophageal cancer occur in the gross tumor volume (GTV). And the metabolic active areas post-treatment were located in the high FDG uptake areas prior to the radiotherapy. The hypothesis is that selective dose boost to the esophageal GTV could be safely delivered using a simultaneous integrated boost (SIB) technique, and that boosting the high 18F-deoxyglucose (FDG) uptake areas of the esophageal GTV defined prior to treatment may improve local tumor control.

Official Title
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Dose Escalation Using a Simultaneous Integrated Boost Technique Based on 18FDG-PET/CT for Unresectable Thoracic Esophageal Cancer: a Phase I/II Trial

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: Chemotherapy (5-FU+DDP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically proven diagnosis of esophageal squamous cell carcinoma. ECOG performance status 0-1. Able to swallow semifluid diet. Patients must not have received either radiotherapy or chemotherapy. Technically unresectable, medically inoperable, or surgery declined by the patient. SUVmax in the pre-treatment FDG-PET scan > 5 for the primary tumor and the length of the primary tumor ≤10cm. Normal liver and renal function and adequate bone marrow reservation. Meet the requirements of the dose limitation to the critical organ: V20≤25%，Dmean≤15Gy for lung; Dmax ≤45Gy for spinal cord，Dmean ≤20Gy for liver. Written, signed informed consent. Exclusion Criteria: Other malignancy histology. Any evidence of visceral metastases. Prior radiotherapy to the thorax or systemic therapy for esophageal cancer. Evidence of deep esophageal ulcer or esophageal perforation. Weight loss ≥10% within half year or cachexia. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ. History of cardiac disease: congestive heart failure > NYHA class 2, active CAD, cardiac arrythmias requiring anti-arrhythmic therapy or uncontrolled hypertension within the last 12 months. Concurrent uncontrolled medical conditions. Pregnant or lactating women. Drug addiction, alcoholism or AIDS. Uncontrolled seizures or psychiatric, behavioural disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: radiotherapy+chemotherapy<br>Radiotherapy: LEVEL 1: dose given at PTV-G and PTV-C will be 64Gy/32 fractions and 50Gy/25 fractions. LEVEL 2: dose given at PTV-G and PTV-C will be 63Gy/28 fractions and 50.4Gy/28 fractions. LEVEL 3: dose given at PTV-GR (with an integrated boost to the 50% SUVmax area of the primary tumor of the pre-treatment 18FDG-PET/CT scan), PTV-G and PTV-C will be 70Gy/28 fractions, 63Gy/28 fractions and 50.4Gy/28 fractions. LEVEL 4: dose given at PTV-GR (with an integrated boost to the 50% SUVmax area of the primary tumor of the pre-treatment 18FDG-PET/CT scan), PTV-G and PTV-C will be 70Gy/25 fractions, 62.5Gy/25 fractions and 50Gy/25 fractions. Chemotherapy: Concurrent chemotherapy: Cisplatin 25mg/m2 IV daily on Days 1-3 and 29-31 plus 5-FU 500mg/m2 IV continuous infusion over 24 hours daily on Days 1-4 and 29-32. Consolidation chemotherapy: Cisplatin 25mg/m2 IV daily on Days 1-3 plus 5-FU 600mg/m2 IV daily on Days 1-5, cycled every 4 weeks for 2 cycles. | Radiation: Radiotherapy<br>* Patients will receive from 5 to 6 weeks 5 days a week radiations. The dose of radiation will depend on the level they will be included.<br>Drug: Chemotherapy (5-FU+DDP)<br>* Patients will receive 2 cycles of concurrent chemotherapy (cisplatin 25mg/m2 IV daily on Days 1-3 and 29-31 plus 5-FU 500mg/m2 IV continuous infusion over 24h daily on Days 1-4 and 29-32) during radiotherapy period. Consolidation chemotherapy (cisplatin 25mg/m2 IV daily on Days 1-3 plus 5-FU 600mg/m2 IV daily on Days 1-5, cycled every 4 weeks) will be given for 2 cycles one month after the end of radiochemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity(DLT) |  | 3 months after the finish of the radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | 3 years | 
| Progression-free survival (PFS) |  | 3 years | 
| Failure patterns |  | 3 years | 
| Late toxicity | Esophageal perforation, esophageal bleeding or late radiation-induced lung or heart injury of grade 3 or above(CTCAE3.0) | 3 years |