Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Overview

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.

Full Title of Study: “Randomized Clinical Trial Comparing the Timing of Resective Surgery After Neoadjuvant Chemoradiotherapy in Cancer of the Esophagus or Gastric Cardia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 19, 2019

Interventions

  • Procedure: Resective surgery

Arms, Groups and Cohorts

  • Active Comparator: Resective surgery after 4-6 weeks
    • Resective surgery 4-6 weeks after completed chemoradiotherapy (CRT)
  • Active Comparator: Resective surgery after 10-12 weeks
    • Resective surgery 10-12 weeks after completed chemoradiotherapy (CRT)

Clinical Trial Outcome Measures

Primary Measures

  • Complete histological response proportion, using the Chirieac grading system.
    • Time Frame: analysis is completed 4 weeks after surgery

Secondary Measures

  • Overall primary tumor treatment response defined as complete histological response (Chirieac 0) and partial histological response (Chirieac 1 and 2) together.
    • Time Frame: analysis is completed 4 weeks after surgery
  • ypN tumor status, classified as ypN0 to ypN3.
    • Time Frame: analysis is completed 4 weeks after surgery
  • 5 year survival by intention to treat and per protocol analyses in each study arm.
    • Time Frame: 5 years
  • Proportion of disease free patients after 5 years by intention to treat and per protocol analyses in each study arm.
    • Time Frame: 5 years
  • R0 resection rate in each study arm.
    • Time Frame: analysis is completed 4 weeks after surgery
  • Resectability rate in each study arm.
    • Time Frame: 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)
    • Time Frame: 4-6 or 10-12 weeks after completed CRT
    • According to Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
  • Postoperative complications in each study arm.
    • Time Frame: 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).
    • Time Frame: 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.
  • QUALYs at 5 year follow-up in each study arm.
    • Time Frame: 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.
  • Correlation between symptom scores, endoscopy and radiology; and complete histological response.
    • Time Frame: 4 weeks after surgery
  • Nutritional status of patients in each study arm.
    • Time Frame: within a week before the start of CRT, within a week before surgery and 5 years after surgery

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Karolinska University Hospital
  • Collaborator
    • Oslo University Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Magnus Nilsson, Associate professor – Karolinska University Hospital
  • Overall Official(s)
    • Magnus Nilsson, Prof, Principal Investigator, Karolinska University Hospital

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