Phase II Trial of Thalidomide Combined With Concurrent Chemoradiotherapy in Esophageal Cancer

Changzhou No.2 People's Hospital180 enrolled

Overview

The purpose of this study is to down-regulate VEGF expression in esophageal cancer patients by thalidomide, so to improve their chemoradiotherapy effect. Patients with esophageal cancer receiving chemoradiotherapy were divided into different sub-group according to dynamic change of their VEGF level,and those showed increased or unchanged VEGF were added thalidomide at random. Efficacy and side effect of thalidomide combined with chemoradiotherapy were evaluated, and at the same time, activity of thalidomide on esophageal cancer and its clinical safely were assessed.

Radiotherapy:Patients will be conducted CT simulation, and three-dimensional conformal radiation therapy (3DCRT) was performed. 1.8-2.0 Gy/fraction, 5 fractions a week, with a total dose of 60-72Gy will be delivered for all patients by 6-MV-X-ray of linear accelerator. Chemotherapy: Patients will be concurrently administered with irradiation every 4 weeks with PT regimen (cis-platinum of 25 mg/m2/d, d1-4; PTX(paclitaxel)of 135mg/m2/d, d1) for 4 cycles. For the first 2-cycles of chemotherapy they will be concurrently given with irradiation and the remained 2 cycles, after irradiation. Administration of thalidomide: Determine serum VEGF level of the esophageal cancer patients 3-4 weeks after the beginning of radiotherapy, those whose VEGF level, compared with that before radiotherapy, increased or unchanged will be divided into two groups: one is given thalidomide concurrent with the following chemoradiotherapy, 100mg/d at bedtime for the initial week, and if no moderate above side effect occurred 200mg/d from the next week till the end of chemoradiotherapy; the other received concurrent chemoradiotherapy only. VEGF determination: Peripheral venous blood samples will be taken in one week before, 3-4 weeks during, and in one week after radiotherapy respectively. The serum VEGF will be determined by the double antibody sandwich ELISA.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Interventions

chemoradiotherapyOTHER

Patients only receive concurrent chemoradiotherapy if their serum VEGF level decrease.

thalidomideDRUG

Patients will be given thalidomide combined with concurrent chemoradiotherapy if their serum VEGF level increase or unchanged.

without thalidomideOTHER

Patients only receive concurrent chemoradiotherapy if their serum VEGF level increase or unchanged

Eligibility

Sex: ALLMin age: 20 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * cytologically or histologically confirmed esophageal carcinoma * age of 20 -80 * Karnofsky performance status ≥ 70 * no treatments prior to enrollment * at least one measurable lesion on CT, MRI or esophageal barium exam * normal functions of heart, lung, liver, kidney and bone marrow * blood exams qualified for chemotherapy, which included hemoglobulin ≥9 g/dl, neutrophil ≥1.5×109/L and platelet (PLT) ≥100×109/L, creatinine ≤1.5 UNL * informed consent signed Exclusion Criteria: * prior treatments of chemotherapy or irradiation * poor bone marrow, liver and kidney functions, which would make chemotherapy intolerable * contraindication for irradiation: complete obstruction of esophagus, deep esophageal ulcer, fistula to mediastinum, or haematemesis * participating in other clinical trials * pregnancy, breast feeding, or not adopting birth control * drug or alcohol addiction, uncontrolled epileptic seizure, or psychotic with no ability of self control * coexisted morbidities that investigators believed not suitable for chemoradiation

Outcomes

Primary Outcomes

Treatment efficacy

Treatment efficacy were evaluated by the indexes as Locoregional tumor response. Locoregional tumor response will be evaluated 3 months after completion of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST).

Time frame: 3 months after completion of treatment

Secondary Outcomes

Overall survival (OS)

Overall survival (OS) will be evaluated 1 year and 3 years after completion of treatment using Kaplan-Meier model.

Time frame: 1 year and 3 years after completion of treatment

Local progression-free survival (LPFS)

1 year and 3 years after completion of treatment using Kaplan-Meier model.

Time frame: 1 year and 3 years after completion of treatment

Safety

All patients are to be estimated Quality Of Life(such as dizzy, somnolence, queasiness and vomit,anaphylaxis incidence) ,acute radiation reactions such as acute radiation esophagitis and tracheitis incidence(evaluated by the Radiation Therapy Oncology Group (RTOG) toxicity criteria),complete blood cell count(such as leukocyte, neutrophil,hemoglobulin, platelet level), serum biochemistry(such as creatinine level).

Time frame: 1 week after completion of treatment