Radiation Dose Escalation in Esophageal Cancer

Study Overview
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Brief Summary
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The aim of this trial is to find the maximum tolerable dose of radiation that can be delivered combined with chemotherapy (DDP & Paclitaxel) in patients with inoperable or medically unresectable esophageal cancer.

Detailed Description
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The RTOG 8501 has established concurrent radiochemotherapy as the standard of care for cancer of the esophagus.However, locoregional 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.

Official Title
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Phase I Trial of Radiation Dose Escalation With Concurrent Weekly Cisplatin and Paclitaxel in Patients With Esophageal Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Radiation: radiochemotherapy 1
* Radiation: radiochemotherapy 2
* Radiation: radiochemotherapy 3
* Radiation: radiochemotherapy 4
* Radiation: radiochemotherapy 5
* Radiation: radiochemotherapy 6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary squamous cell carcinoma of the esophagus Age 1 8-75. Patients must be deemed unresectable disease or patient is not deemed operable due to medical reasons. Patients with distant metastasis and life expectancy >/= 3 months are eligible. Zubrod performance status 0 to 2 No prior radiation to the thorax that would overlap with the current treatment field. Patients with nodal involvement are eligible 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. A signed informed consent must be obtained prior to therapy. 1 0. Induction chemotherapy is allowed. Exclusion Criteria: The presence of a fistula. Prior radiotherapy that would overlap the radiation fields. gastroesophageal junction cancer. Uncontrolled concurrent illness including, but not limited to: Chronic 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. Known hypersensitivity to paclitaxel. 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. Conditions precluding medical follow-up and protocol compliance

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Dose Limiting Toxicities (DLTs) Occurring in Participants | The DLTs were defined as grade >/=4 esophatitis, any other grade >/=3 nonhematological toxicity (except nausea and vomiting), or grade >/=4 hematological toxicity lasting more than 7 days, which are possibly, probably, or definitely associated with protocol treatment occurring during and after completion of the HFRT boost treatment. | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Failure | Local failure will be assessed radiographically using endoscopy with biopsy, CT scan, and a positron emission computed tomography-CT scan. which was defined as persistence /recurrence of the tumor in the radiation therapy field. | 15 months |