Nordic ORgan Preservation Pilot Approach Nonrandomised Single-Arm Trial for Non-Operative Management of Rectal Cancer

Rectal Cancer Clinical Trial

— NORPPA-1  

Official title:

Nordic ORgan Preservation Pilot Approach - A Nonrandomised Single-Arm Trial for Non-Operative Management of Rectal Cancer (NORPPA-1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06328361
• Other study ID #: R24008
• Status: Recruiting
• Phase: N/A
• Start date: May 16, 2024
• Est. completion date: December 31, 2032

Study information

• Verified date: June 2024
• Source: Tampere University Hospital
• Contact: Toni T Seppälä, MD, PhD
• Phone: +358444722846
• Email: toni.seppala[@]tuni.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2032
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histopathological verification of primary rectal adenocarcinoma

• Complete clinical response at response assessment after neoadjuvant therapy

• Informed consent to organ preservation study

Exclusion Criteria:

• Evidence of metastatic disease (fulfilling M-class criteria of TNM)

• No neoadjuvant therapy

• Inability to understand the information related to harms and benefits

Related Conditions & MeSH terms

• Rectal Adenocarcinoma
• Rectal Cancer
• Rectal Neoplasms

Intervention

Procedure:
• Nonoperative surveillance
Clinical and imaging surveillance with digital rectal examination and/or endoscopy, rectal MRI and body CT

Locations

Country	Name	City	State
Estonia	North Estonia Medical Centre	Tallin
Estonia	West Tallinn Central Hospital	Tallin
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Finland	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

Sponsors (14)

Lead Sponsor	Collaborator
Tampere University Hospital	East Tallinn Central Hospital, Helsinki University Central Hospital, Jyväskylä Central Hospital, Kuopio University Hospital, North Estonia Medical Centre, North Karelia Central Hospital, Oulu University Hospital, Satakunta Central Hospital, Seinajoki Central Hospital, Tampere University, Tartu University Hospital, Turku University Hospital, West Tallinn Central Hospital

Countries where clinical trial is conducted

Estonia,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival	Survival from complete clinical response to locoregional failure or distant metastases	2 years
Secondary	Overall survival	Survival from complete clinical response to death or censoring of observation	5 years
Secondary	TME-free survival	Survival from complete clinical response to total mesorectal excision surgery	5 years
Secondary	ctDNA-free survival	Survival from complete clinical response to positive ctDNA result	5 years
Secondary	Post local regrowth disease-free survival	Survival from operated local regrowth to recurrence	5 years
Secondary	Post local regrowth overall survival	Survival from operated local regrowth to death or censoring of observation	5 years
Secondary	Local regrowth-free survival	Survival from complete clinical response to local regrowth	5 years
Secondary	Local recurrence-free survival	Survival from complete clinical response to local recurrence after local regrowth	5 years
Secondary	Distant metastases-free survival	Survival from complete clinical response to distant metastases	5 years
Secondary	Disease-free survival	Survival from complete clinical response to locoregional failure or distant metastases	5 years
Secondary	Salvage rate after local regrowth	Rate of successful TME surgery, local excision or metastasectomy after local regrowth	5 years
Secondary	Quality of life score	Baseline and change in quality of life after complete clinical response	5 years
Secondary	Complication rates	Clavien-Dindo complications after NOM and after local regrowth and after recurrence	5 years