NCT03381651

Brief Summary

Esophageal cancer is one of the most common cancers worldwide, while more than half new cases and deaths occurred in China. Surgery is the main curative treatment for this disease, the 5-year survival of EC remains poor, since most diseases are diagnosed at advanced stages. In last decades, several large clinical trials and meta-analyses have demonstrated that neo-adjuvant chemoradiotherapy followed by surgery can significantly increase the overall survival of patients with EC compared with surgery alone, while no effect of nCRT was apparent on postoperative health-related quality of life . However, the optimal radiation dose and surgery timing are still unknown. The investigators hypothesize that patients who receive higher dose (50.4Gy/28F) of neoadjuvant chemoradiation will have better pathologic response and progress-free survival compared to lower dose (41.4Gy/23F) of chemoradiation followed by surgery.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
147

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Feb 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 18, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 22, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

February 22, 2018

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2021

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 22, 2023

Completed
Last Updated

November 18, 2024

Status Verified

March 1, 2022

Enrollment Period

3 years

First QC Date

December 18, 2017

Last Update Submit

November 13, 2024

Conditions

Esophageal CarcinomaNeoadjuvant ChemoradiotherapySurgery

Keywords

Radiation dose

Outcome Measures

Primary Outcomes (1)

  • Progression free survival

    Time from randomization to tumor progression or any deaths

    2 year

Secondary Outcomes (5)

  • R0 resection rate in each arm

    analysis is completed 4 weeks after surgery

  • Complete pathological response rate

    analysis is completed 4 weeks after surgery

  • Postoperative complications in each study arm

    30 and 90 days after surgery

  • Treatment failure pattern

    2 year

  • Overall survival

    5 year

Study Arms (2)

Higher dose (50.4Gy/28F) of neoadjuvant chemoradiation

ACTIVE COMPARATOR

Neoadjuvant chemoradiation: RT: 50.4Gy/28F/5.6W; CT: paclitaxel 50mg/m2 d1, qw + CBP AUC2 d1, qw, weekly for 6 wks; Surgery: 4-6 weeks after nCRT

Radiation: Higher dose (50.4Gy/28F) of neoadjuvant chemoradiation

Lower dose (41.4Gy/23F) of neoadjuvant chemoradiation

ACTIVE COMPARATOR

Neoadjuvant chemoradiation: RT: 41.4Gy/23F/4.6W; CT: paclitaxel 50mg/m2 d1, qw + CBP AUC2 d1, qw, weekly for 5 wks; Surgery: 4-6 weeks after nCRT

Radiation: Lower dose (41.4Gy/23F) of neoadjuvant chemoradiation

Interventions

Higher dose (50.4Gy/28F) of neoadjuvant chemoradiationRADIATION

50.4Gy/28F radiation and concurrent chemotherapy with paclitaxel plus CBP used weekly

Higher dose (50.4Gy/28F) of neoadjuvant chemoradiation
Lower dose (41.4Gy/23F) of neoadjuvant chemoradiationRADIATION

41.4Gy/23F radiation and concurrent chemotherapy with paclitaxel plus CBP used weekly

Lower dose (41.4Gy/23F) of neoadjuvant chemoradiation

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age:18-70 years
  • Histologically verified squamous carcinoma of the thoracic esophagus.
  • Patients with performance status 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale at the pre CRT evaluation and judges to be fit for surgery at the pre and post CRT evaluations.
  • Tumors should be resectable or potentially resectable and without distant metastasis, as assessed before neoadjuvant CRT, including clinical stage T2-4N0M0 or T1-4N1M0 according to the 6th AJCC system.
  • Joined the study voluntarily and signed informed consent form
  • No surgical contraindications
  • No serious system dysfunction and immuno-deficiency, Adequate organ function including the following: Hemoglobin ≥10 g/dL, Neutrophils (ANC )≥1.5x109/L, platelet count ≥100x 109/L, TBIL\<1.5 x ULN, ALT and AST ≤ 2.5 x ULN, creatinine≤1.5 x ULN

You may not qualify if:

  • Cervical esophageal cancer (The upper end of the lesion is in the esophagus of the cervical segment).
  • Patients with biopsy (by endoscopic ultrasound, laparoscopy, or laparotomy) proven metastatic supraclavicular or celiac nodes are ineligible.
  • Invasion of the tracheobronchial tree or aorta
  • Tracheoesophageal fistula
  • Concurrent pregnancy or lactation
  • Severe diabetes mellitus with poor blood glucose control
  • History of a second malignancy
  • Patients being unable to undergo esophageal reconstruction with gastric tube, due to prior surgery.
  • Patients undergoing esophageal reconstruction with jejunum.
  • Patients have allergy reaction or contraindications to taxanes.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

Related Publications (7)

  • 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.

    PMID: 21684205BACKGROUND

  • Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.

    PMID: 26254683BACKGROUND

  • Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008 Mar 1;26(7):1086-92. doi: 10.1200/JCO.2007.12.9593.

    PMID: 18309943BACKGROUND

  • Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J; Australasian Gastro-Intestinal Trials Group. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007 Mar;8(3):226-34. doi: 10.1016/S1470-2045(07)70039-6.

    PMID: 17329193BACKGROUND

  • Noordman BJ, Verdam MGE, Lagarde SM, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch OR, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A, Sprangers MAG, van Lanschot JJB. Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial. J Clin Oncol. 2018 Jan 20;36(3):268-275. doi: 10.1200/JCO.2017.73.7718. Epub 2017 Nov 21.

    PMID: 29161204BACKGROUND

  • 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.

    PMID: 22646630BACKGROUND

  • Teoh AY, Chiu PW, Yeung WK, Liu SY, Wong SK, Ng EK. Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial. Ann Oncol. 2013 Jan;24(1):165-71. doi: 10.1093/annonc/mds206. Epub 2012 Aug 10.

    PMID: 22887465BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality TherapyTherapeutics

Study Officials

  • Weimin Mao, M.D.

    Zhejiang Caner Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Head of thoracic surgery

Study Record Dates

First Submitted

December 18, 2017

First Posted

December 22, 2017

Study Start

February 22, 2018

Primary Completion

February 22, 2021

Study Completion

February 22, 2023

Last Updated

November 18, 2024

Record last verified: 2022-03

Locations

CN(2)