Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Not Applicable

• Conditions: Cancer of the Esophagus
• Interventions: Procedure: Resective surgery

• Registration Number: NCT02415101
• Lead Sponsor: Karolinska University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-22
• Study First Submitted QC: 2015-04-08
• Study First Posted: 2015-04-14
• Primary Completion: 2019-04-19
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-04
• Last Update Posted: 2019-09-06
• Study Completion: 2024-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 202

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Resective surgery after 10-12 weeks	Resective surgery	Resective surgery 10-12 weeks after completed chemoradiotherapy (CRT)
Resective surgery after 4-6 weeks	Resective surgery	Resective surgery 4-6 weeks after completed chemoradiotherapy (CRT)

Primary Outcome Measures

Name	Time	Method
Complete histological response proportion, using the Chirieac grading system.	analysis is completed 4 weeks after surgery

Secondary Outcome Measures

Name	Time	Method
Resectability rate in each study arm.	4-6 or 10-12 weeks after completed CRT
Safety and toxicity (only grade 3-5 toxicity will be reported) ety and toxicity (only grade 3-5 toxicity will be reported)	4-6 or 10-12 weeks after completed CRT	According to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
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
QUALYs at 5 year follow-up in each study arm.	5 years after surgery	Quality Adjusted Life Year assesses not only how much longer the treatment will allow the patient to live, but weighs in the quality of life with survival as a composite variable.
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
Correlation between symptom scores, endoscopy and radiology; and complete histological response.	4 weeks after surgery
Nutritional status of patients in each study arm.	within a week before the start of CRT, within a week before surgery and 5 years after surgery
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
Postoperative complications in each study arm.	30 days after surgery	Using the classification in the Swedish National Registry for Gastric and Esopgageal Cancer (NREV), including Clavien-Dindo classification.
Health-related quality of life (HRQOL).	4-6 or 10-12 weeks prior to surgery (at randomization after completed CRT), within a week before surgery, 6 months postoperatively, 12 months postoperatively and then yearly until 5 years of follow-up.	Validated questionnaires that assess patients functions (physical, emotional, social, role and cognitive function), symptoms (e.g. fatique, pain, nausea/vomiting, appetite, dysphagia, eating difficulties and diarrhea) and global quality of life.

Trial Locations

Locations (1)

Department of Surgery Gastrocentrum Karolinska Univeristy Hospital; 🇸🇪 Stockholm, Sweden