Phase III Study of Neo-adjuvant Chemoradiotherapy Followed by Surgery for Squamous Cell Esophageal Cancer

Squamous Cell Esophageal Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01216527
• Other study ID #: 2007048
• Status: Active, not recruiting
• Phase: Phase 3
• First received: October 6, 2010
• Last updated: February 24, 2017
• Start date: June 2007
• Est. completion date: December 2019

Study information

• Verified date: February 2017
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 430
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Esophageal Neoplasms
• Squamous Cell Esophageal Carcinoma

Intervention

Procedure:
• Neo-adjuvant Chemoradiotherapy followed by Surgery
Radiotherapy combined with concomitant chemotherapy: Radiotherapy Program:External radiation with a total dose of 40.0Gy is given in 20 fractions of 2.0Gy,5 fractions a week. neo-chemotherapy program: Vinorelbine 25mg/m2, IV (in the vein) on day 1 and day 8 of each 21 day cycle. Cisplatin 75mg/m2,IV DRIP on day 1 of each 21 day cycle;or Cisplatin 25mg/m2,IV DRIP on day 1 to day 4 of each 21 day cycle. Number of cycles:two surgery:Mckeown Modification Surgery and total two-field lymphadenectomy
• surgery
two field lymphadenectomy

Locations

Country	Name	City	State
China	Sun Yat-sen Uniersity Cancer Center	GuangZhou	Guangdong
China	Cancer Hospital of Shantou University Medical College	Shantou	Guangdong

Sponsors (8)

Lead Sponsor	Collaborator
Sun Yat-sen University	Cancer Hospital of Shantou University, Fudan University, Shanghai Chest Hospital, Taizhou Hospital, The Second People's Hospital of Sichuan, Tianjin Medical University Cancer Institute and Hospital, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Airoldi M, Cortesina G, Giordano C, Pedani F, Bumma C, Gabriele P. Docetaxel and vinorelbine: an effective regimen in recurrent squamous cell esophageal carcinoma. Med Oncol. 2003;20(1):19-24. — View Citation

Herskovic A, Russell W, Liptay M, Fidler MJ, Al-Sarraf M. Esophageal carcinoma advances in treatment results for locally advanced disease: review. Ann Oncol. 2012 May;23(5):1095-103. doi: 10.1093/annonc/mdr433. Review. — View Citation

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):134. — View Citation

Koussis H, Scola A, Bergamo F, Tonello S, Basso U, Karahontzitis P, Chiarion-Sileni V, Pasetto L, Ruol A, Loreggian L, Lora O, Bottin R, Marioni G, Donach M, Jirillo A. Neoadjuvant carboplatin and vinorelbine followed by chemoradiotherapy in locally advanced head and neck or oesophageal squamous cell carcinoma: a phase II study in elderly patients or patients with poor performance status. Anticancer Res. 2008 Mar-Apr;28(2B):1383-8. — View Citation

Kulke MH, Muzikansky A, Clark J, Enzinger PC, Fidias P, Kinsella K, Michelini A, Fuchs CS. A Phase II trial of vinorelbine in patients with advanced gastroesophageal adenocarcinoma. Cancer Invest. 2006 Jun-Jul;24(4):346-50. — View Citation

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group.. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088. — View Citation

Yang H, Fu JH, Hu Y, Lin P, Liu MZ, Li Q, Fang ZC, Hu YH. [Neo-adjuvant chemoradiotherapy followed by surgery in treatment of advanced esophageal carcinoma]. Zhonghua Yi Xue Za Zhi. 2008 Dec 9;88(45):3182-5. Chinese. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival rate		3 and 5 years
Secondary	toxicities of neo-adjuvant chemoradiotherapy	Evaluate the toxicities of neo-adjuvant chemoradiotherapy,according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 3.0(CTC AE3.0).	56 days
Secondary	assessment in perioperation	Removal rate, Time of operation, Quantity of bleeding, Thoracic Drainage, Days of Hospitalization, Rate of Operative Complication, Mortality of perioperation,	perioperative period
Secondary	efficacy of neo-adjuvant chemoradiotherapy	Criteria:Response Evaluation Criteria in Solid Tumors,RECIST	4 weeks after completion of radiotherapy
Secondary	Disease free survival rate		5 years