Nordic ORgan Preservation Pilot Approach Nonrandomised Single-Arm Trial for Non-Operative Management of Rectal Cancer
- Conditions
- Rectal AdenocarcinomaRectal Cancer
- Interventions
- Procedure: Nonoperative surveillance
- Registration Number
- NCT06328361
- Lead Sponsor
- Tampere University Hospital
- Brief Summary
The goal of this one-arm clinical trial is to implement and study the oncological outcomes of nonoperative management of rectal cancer having complete clinical response to neoadjuvant therapy. The main questions to answer are
* if the oncological results of nonoperative management after Nordic practice in chemoradiotherapy indications differ from experiences elsewhere
* what is the organ preservation rate
* what is the local regrowth rate
- Detailed Description
Background: Non-operative management (NOM) for rectal cancer is an accepted treatment option that has not been commonly utilized in Finland but has been widely adopted in major cancer centers worldwide. NOM can be considered if the rectal tumor disappears with neoadjuvant treatment, resulting in a complete clinical response.
Objective: The aim of the study is to establish a unified NOM protocol for national use and determine whether the outcomes of Finnish and Estonian treatment practices align with international experiences.
Design: The study is a prospective, non-randomized, single-arm, international multicenter trial examining the oncological and quality-of-life consequences of NOM.
Primary Endpoint: The primary endpoint is disease-free survival 2 years after the initiation of NOM.
Secondary Endpoints: These include overall survival, disease-specific survival, survival free from total mesorectal excision (TME) surgery, survival free from circulating tumor DNA (ctDNA) detection after complete clinical response, recurrence-free survival, incidence of local recurrence and metastases, salvage TME success rate, quality of life at 1 year post-NOM, and treatment-related morbidity up to 5 years.
Inclusion Criteria: Patients must have histopathologically confirmed primary rectal adenocarcinoma before neoadjuvant treatment, achieve clinical complete response (cCR) after neoadjuvant therapy, and express willingness to undergo rectum-preserving treatment after considering the risk of recurrence.
Exclusion Criteria: Patients with evidence of metastasis at diagnosis, aged under 18, those not receiving neoadjuvant treatment, or those unable to provide informed consent are excluded.
Diagnosis and Treatment: Pretreatment of patients follows standard practice. Upon meeting inclusion criteria with confirmed cCR, patients undergo protocolized monitoring with clinical examination, laboratory tests, and imaging.
Randomization: No randomization is performed.
Follow-up: Patients are monitored every 3 months for the first 2 years, then every 6 months for 3 years. Monitoring replaces surgical intervention unless cancer recurs. Follow-up is part of standard care, with costs covered by the healthcare system.
Safety: Incidence of local recurrence and success of resection post-recurrence are monitored closely. If over 30% local recurrence occurs post-cCR, it may necessitate study termination at the center.
Data Collection: Clinical data are entered into electronic case report forms (eCRFs) based on primary healthcare documentation and stored pseudonymized on the primary research center's server. Molecular and pseudonymized clinical data are collected securely for analysis.
Sample Size Calculation and Statistical Analysis: A sample of 200 patients is estimated to provide sufficient data for the primary and key secondary endpoints and to meet other study objectives accurately.
Data Handling: Data handling adheres to privacy legislation, with information stored pseudonymously.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Histopathological verification of primary rectal adenocarcinoma
- Complete clinical response at response assessment after neoadjuvant therapy
- Informed consent to organ preservation study
- Evidence of metastatic disease (fulfilling M-class criteria of TNM)
- No neoadjuvant therapy
- Inability to understand the information related to harms and benefits
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nonoperative management Nonoperative surveillance The patients presenting with complete clinical response undergo nonoperative management (i.e. watch \& wait) as surveillance for local regrowth or distant spread.
- Primary Outcome Measures
Name Time Method Disease-free survival 2 years Survival from complete clinical response to locoregional failure or distant metastases
- Secondary Outcome Measures
Name Time Method Overall survival 5 years Survival from complete clinical response to death or censoring of observation
Post local regrowth disease-free survival 5 years Survival from operated local regrowth to recurrence
TME-free survival 5 years Survival from complete clinical response to total mesorectal excision surgery
Distant metastases-free survival 5 years Survival from complete clinical response to distant metastases
ctDNA-free survival 5 years Survival from complete clinical response to positive ctDNA result
Post local regrowth overall survival 5 years Survival from operated local regrowth to death or censoring of observation
Local regrowth-free survival 5 years Survival from complete clinical response to local regrowth
Local recurrence-free survival 5 years Survival from complete clinical response to local recurrence after local regrowth
Disease-free survival 5 years Survival from complete clinical response to locoregional failure or distant metastases
Salvage rate after local regrowth 5 years Rate of successful TME surgery, local excision or metastasectomy after local regrowth
Quality of life score 5 years Baseline and change in quality of life after complete clinical response
Complication rates 5 years Clavien-Dindo complications after NOM and after local regrowth and after recurrence
Trial Locations
- Locations (13)
East Tallinn Central Hospital
🇪🇪Tallinn, Estonia
North Estonia Medical Centre
🇪🇪Tallin, Estonia
West Tallinn Central Hospital
🇪🇪Tallin, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
North Karelia Central Hospital
🇫🇮Joensuu, Finland
Jyväskylä Central Hospital
🇫🇮Jyväskylä, Finland
Kuopio University Hospital
🇫🇮Kuopio, Finland
Oulu University Hospital
🇫🇮Oulu, Finland
Satakunta Central Hospital
🇫🇮Pori, Finland
Seinajoki Central Hospital
🇫🇮Seinäjoki, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Turku University Hospital
🇫🇮Turku, Finland