Randomized Clinical Trial Comparing the Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Cancer of the Esophagus or Gastric Cardia

Karolinska University Hospital1 site in 1 country202 target enrollmentFebruary 1, 2015

ConditionsCancer of the Esophagus

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Cancer of the Esophagus
Sponsor: Karolinska University Hospital
Enrollment: 202
Locations: 1
Primary Endpoint: Complete histological response proportion, using the Chirieac grading system.
Status: Completed
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

February 1, 2015

End Date

August 5, 2024

Last Updated

8 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Karolinska University Hospital

Responsible Party

Principal Investigator

Magnus Nilsson

Professor

Karolinska University Hospital

Eligibility Criteria

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 TXNXM
•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.

Outcomes

Primary Outcomes

Complete histological response proportion, using the Chirieac grading system.

Time Frame: analysis is completed 4 weeks after surgery

Secondary Outcomes

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)
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)
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)
R0 resection rate in each study arm.(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)
Postoperative complications in each study arm.(30 days after surgery)
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.)