A Trial Estimating The Optimal Radiation Volume Of Postsurgical Radiation For Patients With Esophageal Cancer

A Randomized Phase II Trial Estimating The Optimal Radiation Volume Of Postsurgical Radiation For Patients With Locoregionally Advanced Thoracic Esophageal Squamous Cell Carcinoma

A randomized phase II trial to estimate the optimal radiation volume of postsurgical radiation for patients with locoregionally advanced thoracic esophageal squamous cell carcinoma (T3-4, any N, M0).

Study Overview

• Status: Unknown
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: fluorouracil; Drug: cisplatin; Radiation: enlarge irradiation volume; Radiation: Small volume radiation

Detailed Description

Patient Population:

Thoracic esophageal squamous cell carcinoma after esophagectomy with at least 15 lymph nodes removed for adequate nodal staging.

T3-4, any N, M0.

Scheme:

After esophagectomy, patients are firstly stratified by 2 factors: (1)number of lymph node metastasis (<3 or >=3) and (2)tumor resection status (R1 resection or R2 resection).

Note: Pathological R0 resection status is required for this study. So here R1 and R2 resection are not actually pathological status of resection, only clinical judgement by physician based on the chest-CT before esophagectomy.

Then patients are randomized to 2 arms:

Arm A:

Large field radiation (tumor bed + ENI (elective nodal irradiation)) + Sequential chemotherapy (4 cycles).

Arm B:

Small field radiation (tumor bed only) + Sequential chemotherapy (4 cycles).

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Cancer Center
      • Contact: Xu-Wei Cai, M.D., Ph.D.; Phone Number: 1504 8621-64175590; Email: birdhome2000@hotmail.com
      • Principal Investigator: Xiao-Long Fu, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 and ≤70
2. Performance status 0-1
3. Weight is not less than 90% of it before operation
4. Registration within 8 weeks after esophagectomy
5. Histologically proven primary thoracic esophageal squamous cell carcinoma
6. R0 resection and number of lymph nodes dissected ≥15 after esophagectomy
7. Pathological stage of T3-4N0-3M0
8. Chest and abdominal contrast enhanced CT within 6 weeks prior to registration(PET/CT scan is selective)
9. Without supraclavicular nodes and abdominal regions nodes existed after surgery
10. Without neo-adjuvant chemotherapy and radiotherapy
11. WBC≥ 4.0X109/L ,Absolute neutrophil count (ANC) ≥ 2.0X109/L
12. Platelets ≥ 100X109/L
13. Hemoglobin ≥ 90g/L(without blood transfusion)
14. AST (SGOT)/ALT (SGPT) ≤ 2.5 x upper limit of normal, Bilirubin ≤ 1.5 x upper limit of normal
15. Creatinine ≤ 1.5 x upper limit of normal
16. Sign study-specific informed consent prior to study entry

Exclusion Criteria:

1. Multiple primary esophageal tumors
2. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).

3. Severe, active comorbidity, defined as follows:

   3.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months 3.2 Transmural myocardial infarction within the last 6 months 3.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration 3.4 Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration 3.5 Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

4. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
5. Prior systemic chemotherapy, prior radiation therapy or prior target drug therapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; After esophagectomy, patients in Arm A will receive Large field radiation (tumor bed + ENI (elective nodal irradiation)) + Sequential chemotherapy	Drug: fluorouracil; Drug: cisplatin; Radiation: enlarge irradiation volume; In Arm A, postsurgical radiation target volume includes tumor bed and elective nodes area
Active Comparator: B; After esophagectomy, patients in Arm B will receive small field radiation (tumor bed only) + Sequential chemotherapy	Drug: fluorouracil; Drug: cisplatin; Radiation: Small volume radiation; In Arm B, postsurgical radiation target volume includes tumor bed only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
Survival	To evaluate if the survival outcome of postsurgical radiation with a small target volume involved tumor bed only is not worse than a large volume (tumor bed and elective nodes) for patients with locoregionally advanced thoracic esophageal squamous cell carcinoma.

Secondary Outcome Measures

Outcome Measure	Measure Description
Safety and Tolerability	To evaluate the incidence rate of adverse events-especially radiation-induced lung toxicity
Failure pattern	To evaluate the rationality of radiation target volumes by analyzing the therapeutic failure patterns especially by comparing the in-field and out-of-field recurrences.

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Zhejiang Cancer Hospital; The First Affiliated Hospital of Anhui Medical University; Fujian Cancer Hospital; RenJi Hospital; The First Affiliated Hospital of Soochow University; Shanghai Chest Hospital; Jiangsu Cancer Institute & Hospital; Shanghai Pulmonary Hospital, Shanghai, China; Zhejiang University; First Affiliated Hospital of Wenzhou Medical University; Affiliated Hospital of Jiangsu University; Anhui Provincial Hospital; The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
• Investigators: Principal Investigator: Xiao-Long Fu, M.D, Ph.D., Fudan University

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: July 8, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 20, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: radiation; esophagectomy; thoracic esophageal squamous cell carcinoma; elective nodal irradiation; tumor bed
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: 2011ESO_FU_01