Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer

NCT02415101 | Completed DMC

• 1 other identifier: 2014/748-31-3
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 1

Brief Summary

This study compares outcomes with regard to the timing of resective surgery after neoadjuvant chemoradiotherapy (CRT) in cancer of the esophagus or gastric cardia. Patients are randomised to surgery either conventional 4-6 or 10-12 weeks after termination of CRT. The study hypothesis is that a longer delay improves histological response and decreases the risk of postoperative morbidity and mortality.

Conditions

Cancer of the Esophagus

Keywords

Adenocarcinoma; Squamous cell carcinoma; Gastroesophageal Junction

Outcome Measures

Primary Outcomes (1)

• Complete histological response proportion, using the Chirieac grading system.

  analysis is completed 4 weeks after surgery

Secondary Outcomes (12)

• Overall primary tumor treatment response defined as complete histological response (Chirieac 0) and partial histological response (Chirieac 1 and 2) together.

  analysis is completed 4 weeks after surgery

• ypN tumor status, classified as ypN0 to ypN3.

  analysis is completed 4 weeks after surgery

• 5 year survival by intention to treat and per protocol analyses in each study arm.

  5 years

• Proportion of disease free patients after 5 years by intention to treat and per protocol analyses in each study arm.

  5 years

• R0 resection rate in each study arm.

  analysis is completed 4 weeks after surgery

Study Arms (2)

Resective surgery after 4-6 weeks

ACTIVE COMPARATOR

Resective surgery 4-6 weeks after completed chemoradiotherapy (CRT)

Procedure: Resective surgery

Resective surgery after 10-12 weeks

ACTIVE COMPARATOR

Resective surgery 10-12 weeks after completed chemoradiotherapy (CRT)

Procedure: Resective surgery

Interventions

Resective surgery PROCEDURE

Resective surgery after 10-12 weeks; Resective surgery after 4-6 weeks

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically verified adenocarcinoma or SCC of the esophagus or GEJ Siewert type I and II.
• Tumors should be resectable and without distant metastasis, as assessed after completed CRT.
• 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.
• Pre CRT tumor stage: T1N1-3M0, T2N0-3M0, T3N0-3,M0, T4aN0-3,M0
• Written informed consent
• Completed at least 80% of the planned chemotherapy and at least 90% of the prescribed radiotherapy dose within the neoadjuvant CRT schedule according to protocol within a period of \<36 days.

You may not qualify if:

• Concomitant malignant diagnosis (excluding non-melanoma skin cancer) \<5 years since current cancer diagnosis.
• Ongoing antitumoral treatment irrespective of time since diagnosis of earlier malignancy.
• Patients being unable to comply with the protocol for reasons of language or cognitive function.
• Tumor stage T1N0, T4bNX or TXNXM1.
• Carcinoma of the upper third of the esophagus (i.e. cervical and uppermost thoracic) for simplicity here defined as upper border of tumor above 22 cm from incisors at endoscopy.
• Clear radiological signs of tumor progression during CRT on CT-scan after completion of CRT. PET is not used in this decision as FDG-activity often increase due to radiotherapy induced inflammation.

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Oslo University Hospital: collaborator
• Lund University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• Region Örebro County: collaborator
• University Hospital, Umeå: collaborator
• St. Olavs University Hospital: collaborator
• University Hospital, Linkoeping: collaborator
• University Hospital of North Norway: collaborator
• University Hospital Cologne: collaborator

Study Sites (1)

Department of Surgery Gastrocentrum Karolinska Univeristy Hospital

Stockholm, 14186, Sweden

Location

Related Publications (1)

• Nilsson K, Klevebro F, Rouvelas I, Lindblad M, Szabo E, Halldestam I, Smedh U, Wallner B, Johansson J, Johnsen G, Aahlin EK, Johannessen HO, Hjortland GO, Bartella I, Schroder W, Bruns C, Nilsson M. Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial: Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer. Ann Surg. 2020 Nov;272(5):684-689. doi: 10.1097/SLA.0000000000004340.

  PMID: 32833767 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Adenocarcinoma; Carcinoma, Squamous Cell

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Study Officials

• Magnus Nilsson, Prof

  Karolinska University 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: Professor

Study Record Dates

• First Submitted: February 22, 2015
• First Posted: April 14, 2015
• Study Start: February 1, 2015
• Primary Completion: April 19, 2019
• Study Completion: August 5, 2024
• Last Updated: September 3, 2025

Record last verified: 2024-03

Locations

SE (1)