Statistical Analysis Plan for the SANO-trial: Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Active Surveillance for Oesophageal Cancer (SANO)

Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Active Surveillance for Oesophageal Cancer (SANO-trial): a Phase-III Stepped-wedge Cluster Randomised Trial

An active surveillance approach is proposed after completion of neoadjuvant chemoradiotherapy (nCRT) for carcinoma of the oesophagus. In this SANO (i.e. Surgery As Needed for Oesophageal cancer) approach, surgical resection is offered only to patients in whom a locoregional regrowth is highly suspected or proven, without distant dissemination. Such an organ-preserving strategy can have great advantages, but is only justified if long-term survival is non-inferior to that of the current standard trimodality approach comprising neoadjuvant chemoradiotherapy followed by standard surgery. The aim of this study is to assess the (cost-)effectiveness (including non-financial costs and survival) of active surveillance for patients with squamous cell- or adenocarcinoma of the oesophagus or oesophago-gastric junction.

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Cancer; Surgical Oncology; Neoadjuvant Chemoradiotherapy; Active Surveillance
• Intervention / Treatment: Procedure: Active surveillance

• Study Type: Interventional
• Enrollment (Actual): 776
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GD
      • Erasmus MC, University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who underwent or are planned to undergo neoadjuvant chemoradiotherapy according to CROSS and are planned to undergo potentially curative surgical resection for histologically proven oesophageal or junctional squamous cell carcinoma or adenocarcinoma are eligible. Whenever pathology is inconclusive but a multidisciplinary expert group concludes oesophageal carcinoma because of radiologically or endosonographically highly suspected lesions, patients are eligible for the study.
• Age ≥18;
• Written, voluntary, informed consent.

Exclusion Criteria:

• Language difficulty, dementia or altered mental status prohibiting the understanding and giving of informed consent and to complete quality of life questionnaires;
• Non-FDG-avid tumour at baseline PET-CT scan;
• Initial treatment with endoscopic resection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active surveillance	Procedure: Active surveillance; Patients enrolled in the active surveillance arm will undergo diagnostic evaluations every 3 months in the first year after completion of neoadjuvant treatment, every 4 months in the second year, every 6 months in the third year and yearly in the 4th and 5th year of follow up, or when symptoms or results of any diagnostic test require shorter assessment intervals. In the active surveillance arm, surgical resection will be offered only to those patients, in whom a locoregional regrowth is highly suspected or proven, without any signs of distant dissemination.
Active Comparator: Standard esophagectomy	Procedure: Active surveillance; Patients enrolled in the active surveillance arm will undergo diagnostic evaluations every 3 months in the first year after completion of neoadjuvant treatment, every 4 months in the second year, every 6 months in the third year and yearly in the 4th and 5th year of follow up, or when symptoms or results of any diagnostic test require shorter assessment intervals. In the active surveillance arm, surgical resection will be offered only to those patients, in whom a locoregional regrowth is highly suspected or proven, without any signs of distant dissemination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	the interval between the moment of achieving cCR (i.e. the moment the patient will start the intervention) and death or last follow-up, with a minimal follow-up of two years after reaching cCR.

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): June 1, 2023
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: MEC 17-392

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No