Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Cancer of the Esophagus Clinical Trial

— NeoResII  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02415101
• Other study ID #: 2014/748-31-3
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2015
• Est. completion date: August 2024

Study information

• Verified date: September 2019
• Source: Karolinska University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 202
• Est. completion date: August 2024
• Est. primary completion date: April 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cancer of the Esophagus
• Esophageal Neoplasms

Intervention

Procedure:
• Resective surgery

Locations

Country	Name	City	State
Sweden	Department of Surgery Gastrocentrum Karolinska Univeristy Hospital	Stockholm

Sponsors (9)

Lead Sponsor	Collaborator
Karolinska University Hospital	Haukeland University Hospital, Lund University Hospital, Oslo University Hospital, Region Örebro County, Sahlgrenska University Hospital, Sweden, St. Olavs Hospital, University Hospital, Linkoeping, University Hospital, Umeå

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete histological response proportion, using the Chirieac grading system.		analysis is completed 4 weeks after surgery
Secondary	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
Secondary	ypN tumor status, classified as ypN0 to ypN3.		analysis is completed 4 weeks after surgery
Secondary	5 year survival by intention to treat and per protocol analyses in each study arm.		5 years
Secondary	Proportion of disease free patients after 5 years by intention to treat and per protocol analyses in each study arm.		5 years
Secondary	R0 resection rate in each study arm.		analysis is completed 4 weeks after surgery
Secondary	Resectability rate in each study arm.		4-6 or 10-12 weeks after completed CRT
Secondary	Safety and toxicity (only grade 3-5 toxicity will be reported) ety and toxicity (only grade 3-5 toxicity will be reported)	According to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0	4-6 or 10-12 weeks after completed CRT
Secondary	Postoperative complications in each study arm.	Using the classification in the Swedish National Registry for Gastric and Esopgageal Cancer (NREV), including Clavien-Dindo classification.	30 days after surgery
Secondary	Health-related quality of life (HRQOL).	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.	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.
Secondary	QUALYs at 5 year follow-up in each study arm.	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.	5 years after surgery
Secondary	Correlation between symptom scores, endoscopy and radiology; and complete histological response.		4 weeks after surgery
Secondary	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