Clinical trial NCT01216527: Phase III Study of Neo-adjuvant Chemoradiotherapy Followed by Surgery for Squamous Cell Esophageal Cancer
Official title: A Phase III, Multicenter Randomized Controlled Study of Neo-adjuvant Chemoradiotherapy Followed by Surgery Versus Surgery for Locally Advanced Squamous Cell Esophageal Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Squamous Cell Esophageal Carcinoma
Keywords: Stage IIB or III squamous cell esophageal carcinoma.
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Affiliated Cancer Hospital of Shantou University Medical College
name: Shanghai Chest Hospital
name: Fudan University
name: Zhejiang Cancer Hospital
name: Taizhou Hospital
name: The Second People's Hospital of Sichuan
name: Tianjin Medical University Cancer Institute and Hospital
First posted: 2010-10-07
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to compare neo-adjuvant chemoradiotherapy followed by surgery versus surgery, in terms of the overall survival time (OS) in patients with Stage IIB or III squamous cell esophageal carcinoma.

Detailed description: Esophageal cancer (EC) is the eighth most common cancers in the world, with more than 480,000 new cases and 400,000 deaths occurred annually worldwide. In China, every year, no matter new cases or deaths account for more than half of the world. Besides, over 90% of Chinese patients have esophageal squamous cell carcinoma (ESCC).

Surgery is the main treatment of this disease, but the prognosis of patients with locally advanced esophageal cancer is rather poor. As a result of surgery alone, the 5-year survival rate of about 25% has not changed significantly in several decades.

Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of EC. Nevertheless, the results of different studies were inconsistent. Recently, the CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increased the overall survival of patients with EC compared with surgery alone. It should be noticed that only 84 cases(23%) of ESCC were enrolled in this trial with potential minimal follow-up of 2 years, which may be not perfect to evaluate the effect of this combined therapy for this tumor type.

Up till now, vinorelbine has no indications for esophageal cancer, although, some studied have reported its effect and feasibility to the therapy of EC. Vinorelbine has similar mechanism with paclitaxel and docetaxel, which are recommended for the chemotherapy of EC by NCCN. They are all classified as antimicrotubule agents, which cause mitotic arrest and eventual cell death through inhibition of microtubule dynamics. In comparison with the taxanes, vinorelbine has obvious advantage of few cardiac toxicity. This should be beneficial to prevent cardiac side effects of chemoradiotherapy, especially for the middle or lower thoracic EC, which account for over 70% of thoracic EC in China. For this group of patients, radiotherapy can hardly avoid cardiac toxicity.

Based on our preliminary study, we have demonstrated the validity and safety of vinorelbine and cisplatin-based neoadjuvant chemoradiotherapy.

We are to carry out a phased III clinical trial to investigate the effect of this multidisciplinary therapy for the overall survival of patients with locally advanced ESCC.

Eligibility criteria: Inclusion Criteria:

1. Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage IIB or III, which is potentially resectable.
2. Patients must not have received any prior anticancer therapy.
3. More than 6 months of expected survival.
4. Age ranges from 18 to 70 years.
5. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney.
6. Karnofsky performance status (KPS) of 90 or more.
7. Signed informed consent document on file.

Exclusion Criteria:

1. Patients are diagnosed or suspected to be allergic to cisplatin or vinorelbine.
2. Patients with concomitant hemorrhagic disease.
3. Pregnant or breast feeding.
4. Inability to use gastric conduit after esophagectomy because of a prior surgery.
5. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more.
6. Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer.

Primary outcomes:
measure: Overall survival rate
timeFrame: 3 and 5 years
Secondary outcomes:
measure: toxicities of neo-adjuvant chemoradiotherapy
timeFrame: 56 days
measure: assessment in perioperation
timeFrame: perioperative period
measure: efficacy of neo-adjuvant chemoradiotherapy
timeFrame: 4 weeks after completion of radiotherapy
measure: Disease free survival rate
timeFrame: 5 years
Other outcomes:
Locations:
city: GuangZhou
country: China
facility: Sun Yat-sen Uniersity Cancer Center
state: Guangdong
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Jian-hua Fu, Professor
role: PRINCIPAL_INVESTIGATOR
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