Comparison Between NCRT and NCT Followed by MIE for Treatment of Locally Advanced Resectable ESCC

NCT03001596 | Completed

• 1 other identifier: CMISG1701
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the outcomes of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy on patients with locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0).

Conditions

Esophageal Squamous Cell Carcinoma Stage cT3-4aN0-1M0

Keywords

Neoadjuvant Chemoradiotherapy; Neoadjuvant Chemotherapy; Minimally Invasive Esophagectomy; Esophageal Squamous Cell Carcinoma（cT3-4aN0-1M0）

Outcome Measures

Primary Outcomes (1)

• Overall survival(OS)

  Up to the date of death of any causes since the date of randomization, up to 36 months

Secondary Outcomes (7)

• Progression-free survival(PFS)

  Up to the date of disease recurrence since the date of randomization, up to 36 months

• Pathological response rate(pCR)

  Up to the date of pathological reports obtained since the date of randomization, up to 12 months

• R0 resection rate

  Up to the date of pathological reports obtained since the date of randomization, up to 12 months

• Positive lymph nodes' number

  Up to the date of pathological reports obtained since the date of randomization, up to 12 months

• Treatment related complications

  Up to 1 month after surgery since the data of randomization, up to 13 months

Study Arms (2)

Neoadjuvant chemoradiotherapy

EXPERIMENTAL

Neoadjuvant chemoradiotherapy (NCRT) is performed followed by minimally invasive esophagectomy in enrolled patients.

Procedure: Neoadjuvant Chemoradiotherapy; Procedure: Minimally Invasive Esophagectomy

Neoadjuvant chemotherapy

ACTIVE COMPARATOR

Neoadjuvant chemotherapy (NCT) is performed followed by minimally invasive esophagectomy in enrolled patients.

Procedure: Neoadjuvant Chemotherapy; Procedure: Minimally Invasive Esophagectomy

Interventions

Neoadjuvant Chemoradiotherapy PROCEDURE

Before surgery, patients in this group receive neoadjuvant chemoradiotherapy. A total dose of 40 Gy is delivered in 20 fractions (5 fractions per week) for 4 weeks. Chemotherapy is delivered concomitantly and composed of four cycles of paclitaxel 50mg per square meter of body-surface area and cisplatin 25mg per square meter of body-surface area weekly at the intervals of radiotherapy. After neoadjuvant therapy of 4-8 weeks, minimally invasive esophagectomy is performed.

Also known as: Preoperative Chemoradiotherapy

Neoadjuvant chemoradiotherapy

Neoadjuvant Chemotherapy PROCEDURE

Before surgery, patients in this group receive neoadjuvant chemotherapy. Chemotherapy is delivered and composed of two cycles of paclitaxel 135mg per square meter of body-surface area and cisplatin 75mg per square meter of body-surface area every 4 weeks. After neoadjuvant therapy of 4-8 weeks, minimally invasive esophagectomy is performed.

Also known as: Preoperative Chemotherapy

Neoadjuvant chemotherapy

Minimally Invasive Esophagectomy PROCEDURE

After neoadjuvant therapy, patients in groups receive minimally invasive esophagectomy

Also known as: MIE

Neoadjuvant chemoradiotherapy; Neoadjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed squamous cell carcinoma of the esophagus;
• Tumors of the esophagus are located in the thoracic cavity;
• Pre-treatment stage as cT3-4aN0-1M0 (AJCC/UICC 7th Edition) (In case of stage cT4a, curative resectability has to be explicitly verified by the local surgical investigator prior to randomization).
• Age is between 18 years and 75 years,
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %.
• Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests.
• Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
• Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN);
• Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L)；
• The patient has provided written informed consent and is able to understand and comply with the study;

You may not qualify if:

• Patients with non-squamous cell carcinoma histology;
• Patients with advanced inoperable or metastatic esophageal cancer;
• Pre-treatment stage as cT1-2N0-1M0 (AJCC/UICC 7th Edition);
• Pre-treatment stage as cN2-3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 7th Edition);
• Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator.
• Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
• Pregnant or lactating women and fertile women who will not be using contraception during the trial;
• Allergy to any drugs;
• Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
• Expected lack of compliance with the protocol.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Fujian Medical University Union Hospital: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator
• Ruijin Hospital: collaborator
• Shanghai Chest Hospital: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Changzhi Medical College: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Peking University Cancer Hospital and Institute: collaborator

Study Sites (1)

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (30)

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• Shen Y, Zhong M, Wu W, Wang H, Feng M, Tan L, Wang Q. The impact of tidal volume on pulmonary complications following minimally invasive esophagectomy: a randomized and controlled study. J Thorac Cardiovasc Surg. 2013 Nov;146(5):1267-73; discussion 1273-4. doi: 10.1016/j.jtcvs.2013.06.043. Epub 2013 Aug 28.

  PMID: 23993028 BACKGROUND

• Feng M, Shen Y, Wang H, Tan L, Zhang Y, Khan MA, Wang Q. Thoracolaparoscopic esophagectomy: is the prone position a safe alternative to the decubitus position? J Am Coll Surg. 2012 May;214(5):838-44. doi: 10.1016/j.jamcollsurg.2011.12.047. Epub 2012 Mar 13.

  PMID: 22421259 BACKGROUND

• Shen Y, Zhang Y, Tan L, Feng M, Wang H, Khan MA, Liang M, Wang Q. Extensive mediastinal lymphadenectomy during minimally invasive esophagectomy: optimal results from a single center. J Gastrointest Surg. 2012 Apr;16(4):715-21. doi: 10.1007/s11605-012-1824-7. Epub 2012 Jan 19.

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  PMID: 26254683 RESULT

• Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011 Jul;12(7):681-92. doi: 10.1016/S1470-2045(11)70142-5. Epub 2011 Jun 16.

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• Jang R, Darling G, Wong RK. Multimodality approaches for the curative treatment of esophageal cancer. J Natl Compr Canc Netw. 2015 Feb;13(2):229-38. doi: 10.6004/jnccn.2015.0029.

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• Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014 Aug 10;32(23):2416-22. doi: 10.1200/JCO.2013.53.6532. Epub 2014 Jun 30.

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• Kumagai K, Rouvelas I, Tsai JA, Mariosa D, Klevebro F, Lindblad M, Ye W, Lundell L, Nilsson M. Meta-analysis of postoperative morbidity and perioperative mortality in patients receiving neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal and gastro-oesophageal junctional cancers. Br J Surg. 2014 Mar;101(4):321-38. doi: 10.1002/bjs.9418. Epub 2014 Feb 3.

  PMID: 24493117 RESULT

• Biere SS, van Berge Henegouwen MI, Maas KW, Bonavina L, Rosman C, Garcia JR, Gisbertz SS, Klinkenbijl JH, Hollmann MW, de Lange ES, Bonjer HJ, van der Peet DL, Cuesta MA. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet. 2012 May 19;379(9829):1887-92. doi: 10.1016/S0140-6736(12)60516-9. Epub 2012 May 1.

  PMID: 22552194 RESULT

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• Wang H, Tang H, Fang Y, Tan L, Yin J, Shen Y, Zeng Z, Zhu J, Hou Y, Du M, Jiao J, Jiang H, Gong L, Li Z, Liu J, Xie D, Li W, Lian C, Zhao Q, Chen C, Zheng B, Liao Y, Li K, Li H, Wu H, Dai L, Chen KN. Morbidity and Mortality of Patients Who Underwent Minimally Invasive Esophagectomy After Neoadjuvant Chemoradiotherapy vs Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Surg. 2021 May 1;156(5):444-451. doi: 10.1001/jamasurg.2021.0133.

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Related Links

• Wiley
• American society of clinical oncology
• American society of clinical oncology
• NCCN
• Wiley
• Wolters kluwer
• Springer
• Atypon
• Springer
• AME
• Springer
• Springer
• Wiley

MeSH Terms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Lijie Tan, MD

  Shanghai Zhongshan Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2016
• First Posted: December 23, 2016
• Study Start: January 1, 2017
• Primary Completion: February 1, 2019
• Study Completion: August 1, 2020
• Last Updated: September 10, 2020

Record last verified: 2020-09

Locations

CN (1)