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

NCT ID: NCT01216527

Last Updated: 2017-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

430 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2019-12-31

Brief Summary

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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

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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.

Conditions

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Squamous Cell Esophageal Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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experimental group

Neo-adjuvant Chemoradiotherapy followed by Surgery

Group Type EXPERIMENTAL

Neo-adjuvant Chemoradiotherapy followed by Surgery

Intervention Type PROCEDURE

1. 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
2. surgery:Mckeown Modification Surgery and total two-field lymphadenectomy

control group

only Surgery

Group Type ACTIVE_COMPARATOR

surgery

Intervention Type PROCEDURE

two field lymphadenectomy

Interventions

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Neo-adjuvant Chemoradiotherapy followed by Surgery

1. 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
2. surgery:Mckeown Modification Surgery and total two-field lymphadenectomy

Intervention Type PROCEDURE

surgery

two field lymphadenectomy

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Affiliated Cancer Hospital of Shantou University Medical College

OTHER

Sponsor Role collaborator

Shanghai Chest Hospital

OTHER

Sponsor Role collaborator

Fudan University

OTHER

Sponsor Role collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role collaborator

Taizhou Hospital

OTHER

Sponsor Role collaborator

The Second People's Hospital of Sichuan

OTHER

Sponsor Role collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Jianhua Fu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jian-hua Fu, Professor

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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Sun Yat-sen Uniersity Cancer Center

Guangzhou, Guangdong, China

Site Status

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, China

Site Status

Countries

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China

References

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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. Epub 2011 Feb 4.

Reference Type BACKGROUND
PMID: 21296855 (View on PubMed)

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):1095-1103. doi: 10.1093/annonc/mdr433. Epub 2011 Oct 14.

Reference Type BACKGROUND
PMID: 22003242 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22646630 (View on PubMed)

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. doi: 10.1080/07357900600705268.

Reference Type BACKGROUND
PMID: 16777685 (View on PubMed)

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. doi: 10.1385/MO:20:1:19.

Reference Type BACKGROUND
PMID: 12665680 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18505084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19171088 (View on PubMed)

Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J. Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial. JAMA Surg. 2021 Aug 1;156(8):721-729. doi: 10.1001/jamasurg.2021.2373.

Reference Type DERIVED
PMID: 34160577 (View on PubMed)

Liu S, Wen J, Yang H, Li Q, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Zhao L, Liu H, Hu Y, Liu M, Fu J, Xi M. Recurrence patterns after neoadjuvant chemoradiotherapy compared with surgery alone in oesophageal squamous cell carcinoma: results from the multicenter phase III trial NEOCRTEC5010. Eur J Cancer. 2020 Oct;138:113-121. doi: 10.1016/j.ejca.2020.08.002. Epub 2020 Aug 30.

Reference Type DERIVED
PMID: 32877795 (View on PubMed)

Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.

Reference Type DERIVED
PMID: 30089078 (View on PubMed)

Wen J, Yang H, Liu MZ, Luo KJ, Liu H, Hu Y, Zhang X, Lai RC, Lin T, Wang HY, Fu JH. Gene expression analysis of pretreatment biopsies predicts the pathological response of esophageal squamous cell carcinomas to neo-chemoradiotherapy. Ann Oncol. 2014 Sep;25(9):1769-1774. doi: 10.1093/annonc/mdu201. Epub 2014 Jun 6.

Reference Type DERIVED
PMID: 24907633 (View on PubMed)

Other Identifiers

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2007048

Identifier Type: -

Identifier Source: org_study_id

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