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

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

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.

Study Overview

• Status: Unknown
• Conditions: Esophageal Cancer
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Chemotherapy (5-FU+DDP)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histopathologically proven diagnosis of esophageal squamous cell carcinoma.
2. ECOG performance status 0-1.
3. Able to swallow semifluid diet.
4. Patients must not have received either radiotherapy or chemotherapy.
5. Technically unresectable, medically inoperable, or surgery declined by the patient.
6. SUVmax in the pre-treatment FDG-PET scan > 5 for the primary tumor and the length of the primary tumor ≤10cm.
7. Normal liver and renal function and adequate bone marrow reservation.
8. 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.
9. Written, signed informed consent.

Exclusion Criteria:

1. Other malignancy histology.
2. Any evidence of visceral metastases.
3. Prior radiotherapy to the thorax or systemic therapy for esophageal cancer.
4. Evidence of deep esophageal ulcer or esophageal perforation.
5. Weight loss ≥10% within half year or cachexia.
6. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.
7. 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.
8. Concurrent uncontrolled medical conditions.
9. Pregnant or lactating women.
10. Drug addiction, alcoholism or AIDS.
11. Uncontrolled seizures or psychiatric, behavioural disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: radiotherapy+chemotherapy; 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; 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.; Drug: Chemotherapy (5-FU+DDP); 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)		3 years
Overall survival (OS)		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

Other Outcome Measures

Outcome Measure	Time Frame
Local recurrent rate within the >50% SUVmax region of the primary tumor	3 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Xiaolong Fu, MD, Fudan University

Publications and helpful links

General Publications

• Yu W, Cai XW, Liu Q, Zhu ZF, Feng W, Zhang Q, Zhang YJ, Yao ZF, Fu XL. Safety of dose escalation by simultaneous integrated boosting radiation dose within the primary tumor guided by (18)FDG-PET/CT for esophageal cancer. Radiother Oncol. 2015 Feb;114(2):195-200. doi: 10.1016/j.radonc.2014.12.007. Epub 2015 Jan 10.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: April 24, 2013
• First Submitted That Met QC Criteria: April 26, 2013
• First Posted (Estimate): April 30, 2013

Study Record Updates

• Last Update Posted (Estimate): April 30, 2013
• Last Update Submitted That Met QC Criteria: April 26, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• 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: 2013ESO_FU_01