PET/CT-directed Hyperfractionated Radiation Dose Escalation in Esophageal Cancer

Phase I Study of PET/CT-directed Hyperfractionated Radiation Dose Escalation With Concurrent Weekly Carboplatin and Paclitaxel in Esophageal Cancer

The goal of this study is to find the maximum tolerable dose of radiation that can be delivered with concurrent chemotherapy (carboplatin & paclitaxel) in patients with esophageal cancer.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Radiation: radiochemotherapy 1; Radiation: radiochemotherapy 2; Radiation: radiochemotherapy 3; Radiation: radiochemotherapy 4; Radiation: radiochemotherapy 5; Radiation: radiochemotherapy 6

Detailed Description

Concurrent chemoradiotherapy is the standard of care for esophageal cancer based on the results of phase III randomised trials. The current standard radiation therapy dose has remained 50 Gy at -2 Gy/fraction for decades.However, locoregional control remain problematic, with 25% of patients having persistence and 20% relapse of locoregional disease following the combined modality approach. New regimen is urgently needed for improving localregional control and survival.Investigators hypothesize that hyperfractionated radiation dose escalation to residual tumor volumes after standard chemoradiotherapy as defined by positron emission tomography (PET) /computed tomography (CT) would improve local control and overall survival while reducing the acute and late normal tissue toxicity.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Genernal Hospital

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. Histologically confirmed primary squamous cell carcinoma of the esophagus
2. Age 1 8-75.
3. Patients must be deemed unresectable disease or patient is not deemed operable due to medical reasons.
4. Patients with distant metastasis and life expectancy >/= 3 months are eligible.
5. Zubrod performance status 0 to 2
6. No prior radiation to the thorax that would overlap with the current treatment field.
7. Patients with nodal involvement are eligible
8. Adequate bone marrow, renal and hepatic functions as assessed by the following: Hemoglobin >/= 10.0 g/dl, Platelet count >/= 1 00,000/mm^3,absolute granulocyte count (AGC) ≥2 × 10^9 cells/L,bilirubin and Aspartate transaminase ≤1.5 ×upper limit of normal (ULN), Creatinine </=1 .5 times ULN.
9. A signed informed consent must be obtained prior to therapy. 1 0. Induction chemotherapy is allowed

Exclusion Criteria:

1. The presence of a fistula.
2. Prior radiotherapy that would overlap the radiation fields.
3. gastroesophageal junction cancer.
4. Uncontrolled concurrent illness including, but not limited to: Chronic 5.Obstructive Pulmonary Disease(COPD) exacerbation or other respiratory illness, serious uncontrolled infection, symptomatic congestive heart failure (CHF),unstable angina pectoris, uncontrolled hypertension,or psychiatric illness/social situations that would limit compliance with the study requirements.

6.Known hypersensitivity to paclitaxel. 7.Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.

Acquired Immune Deficiency Syndrome. 8.Conditions precluding medical follow-up and protocol compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: radiochemotherapy 1; Patients will be treated with radiation therapy 57.2 Gy.	Radiation: radiochemotherapy 1; concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 7.2 Gy at 1.2 Gy/Fx/bid to residual tumor volume as defined by PET/CT; concurrent chemotherapy: carboplatin, area under the curve (AUC) 1.5-2, weekly; paclitaxel, 45-50 mg/m2, weekly; Other Names: concurrent radiochemotherapy 1
Experimental: radiochemotherapy 2; Patients will be treated with radiation therapy 64.4 Gy.	Radiation: radiochemotherapy 2; concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 14.4 Gy at 1.2 Gy/Fx/bid to residual tumor volume as defined by PET/CT; Other Names: concurrent radiochemotherapy 2
Experimental: radiochemotherapy 3; Patients will be treated with radiation therapy 71.6 Gy.	Radiation: radiochemotherapy 3; concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 21.6 Gy at 1.2 Gy/Fx/bid to residual tumor volume as defined by PET/CT; Other Names: concurrent chemoradiotherapy regimen 3
Experimental: radiochemotherapy 4; Patients will be treated with radiation therapy 78.8 Gy.	Radiation: radiochemotherapy 4; concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 28.8 Gy at 1.2 Gy/Fx/bid to residual tumor volume as defined by PET/CT; Other Names: concurrent chemoradiotherapy regimen 4
Experimental: radiochemotherapy 5; Patients will be treated with radiation therapy 86 Gy.	Radiation: radiochemotherapy 5; concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 36 Gy at 1.2 Gy/Fx/bid to residual tumor volume as defined by PET/CT; Other Names: concurrent chemoradiotherapy regimen 5
Experimental: radiochemotherapy 6; Patients will be treated with radiation therapy 93.2 Gy.	Radiation: radiochemotherapy 6; concurrent radiochemotherapy: radiotherapy dose level 1: 50 Gy at 2 Gy/Fx/d, then 43.2 Gy at 1.2 Gy/Fx/bid to residual tumor volume as defined by PET/CT; Other Names: concurrent chemoradiotherapy regimen 6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	Maximum Tolerated Dose is defined as CTCAE 4 grade 3 acute radiation-related toxicity	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Local Failure	Local control will be assessed radiographically using endoscopy with biopsy and a positron emission computed tomography-CT scan	2 years

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Study Director: Tingfeng Chen, MD, the ethic committee of shanghai genernal hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): January 10, 2019
• Study Completion (Actual): February 2, 2019

Study Registration Dates

• First Submitted: April 10, 2017
• First Submitted That Met QC Criteria: April 10, 2017
• First Posted (Actual): April 13, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2019
• Last Update Submitted That Met QC Criteria: April 4, 2019
• Last Verified: April 1, 2018

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: SGH201713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No