High Versus Lower Intensity Surveillance Following Resection of Retroperitoneal Sarcoma

Official title

An International, Partially-randomised, Patient-preference Trial Within a Registry of High Versus Lower Intensity Radiological Surveillance Following Primary Resection of Retroperitoneal, Abdominal and Pelvic Soft Tissue Sarcoma

Overview

The SARveillance trial is an efficient, pragmatic, multi-centre, international, stratified, partially-randomised, patient-preference trial within a registry of high versus lower intensity radiological surveillance following primary resection of retroperitoneal, abdominal and pelvic soft tissue sarcoma. The trial design is stratified by sarcoma tumour grade (high/intermediate grade and low grade).

Detailed description

The SARveillance trial is an efficient, pragmatic, multi-centre, international, stratified, partially-randomised, patient-preference trial within a registry of high versus lower intensity radiological surveillance following primary resection of retroperitoneal, abdominal and pelvic soft tissue sarcoma. The trial design is stratified by sarcoma tumour grade (high/intermediate grade and low grade). Both high and lower intensity follow-up represent current practice in different centres across the trial delivery network, with variation at a centre and surgeon level. SARveillance is co-produced in deep collaboration with a patient advisory group. The delivery network is trans-continental including major sarcoma centres in Europe, Asia, and the Americas with central coordination from Istituto Nazionale Tumori, Milan, Italy and Birmingham Centre for Observational and Prospective Studies (BiCOPS) University of Birmingham, UK. For centres that would otherwise be precluded from participating in SARveillance due to institutional level data sharing restrictions, provision has been made for prearranged Individual Participant Data Meta-Analysis (IPDMA). The IPDMA essentially replicates the instruments and processes of SARveillance at a single site level and allows for the PI to provide data for meta-analysis at the close of SARveillance, rather than sharing real-time data with the SARveillance servers at the coordinating institutions. Adult patients undergoing primary resection for retroperitoneal, abdominal and pelvic sarcoma will be eligible for inclusion. The trial design is innovative and efficient, implemented as a trial within an international registry, and adopting concepts from the pragmatic REaCT trial design methodology. Patients that are willing to be randomised will be allocated in a 1:1 ratio to a high or lower intensity follow-up schedule. For patients that decline randomisation, the trial has patient preference arms to maximise insight into decision-making processes in the context of a rare disease and maximise participant recruitment. The primary outcome measure is quality of life, measured as emotional functioning (EF) up to 5 years after surgery, measured 3-monthly, using the questions relating to the EF domain of the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30). Secondary outcomes for the trial will be overall survival up to 5 years after surgery, the cancer worry scale (EORTC library), health utility calculated using EuroQol Group EQ-5D-5L and cost-effectiveness health utility, measured using EQ-5D-5L. The primary outcome measure for low grade tumours is health utility. Pre-planned sub-studies will be conducted including an economic analysis, and validation study for a prognostic risk model.

Interventions

• Diagnostic test High-intensity radiological surveillance
  The standard approach to surveillance imaging will be contrasted CT (IV and oral contrast) of the chest, abdomen and pelvis. All patients require radiological assessment of the chest, abdomen and pelvis at each surveillance round. Tolerance will be given in the protocol for selected patients where CT is not suitable to receive alternative imaging such as MRI or combination of MRI and CT. Uncontrasted CT imaging is permissible where renal toxicity or allergy from intravenous contrast is of concer
• Diagnostic test Lower-intensity radiological surveillance
  The standard approach to surveillance imaging will be contrasted CT (IV and oral contrast) of the chest, abdomen and pelvis. All patients require radiological assessment of the chest, abdomen and pelvis at each surveillance round. Tolerance will be given in the protocol for selected patients where CT is not suitable to receive alternative imaging such as MRI or combination of MRI and CT. Uncontrasted CT imaging is permissible where renal toxicity or allergy from intravenous contrast is of concer

Primary outcome measures

• Emotional Functioning [Time frame: 5 years]

Secondary outcome measures (3)

• Overall survival [Time frame: 5 years]
• Cancer worry scale [Time frame: 5 years]
• Health utility [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Adult patients (greater than 18 years)
• Primary resection
• Histologically confirmed retroperitoneal, abdominal or pelvic soft tissue sarcoma
• R0/R1 resection
• Eligible whether or not the participant undergoes neoadjuvant treatment

Exclusion criteria

• Metastatic disease at time of randomisation
• Recurrent, metastatic or residual disease identified on baseline CT imaging (3-4 months post primary resection)
• Reoperation for recurrent soft tissue sarcoma
• Re-resection following previous inadequate surgery
• R2 resection
• Patients receiving adjuvant therapy that will delay, interrupt or render radiological surveillance unpredictable
• Uterine sarcomas, gastrointestinal stromal tumour (GIST), fibromatosis, epithelial tumours, multifocal disease, sarcomas of bony origin
• Patient declined to consent to data sharing with RESAR (unless in a centre contributing via pre-planned IPDMA)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan

United Kingdom · 1 center

• University Hospitals Birmingham NHS Foundation Trust — Birmingham

Publications

• Whitaker J, Nessim C, Almond M, Ford SJ. Surveillance Post Surgery for Retroperitoneal Soft Tissue Sarcoma. Curr Oncol. 2023 Feb 26;30(3):2781-2791. doi: 10.3390/curroncol30030211. PMID 36975424
• Baia M, Ford SJ, Dumitra S, Sama L, Naumann DN, Spolverato G, Callegaro D. Follow-up of patients with retroperitoneal sarcoma. Eur J Surg Oncol. 2023 Jun;49(6):1125-1132. doi: 10.1016/j.ejso.2022.02.016. Epub 2022 Mar 4. PMID 35277304

Identifiers

NCT: NCT06480396 · INT201/16(05/23)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗