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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer; Rectal Adenocarcinoma
• Intervention / Treatment: Procedure: Nonoperative surveillance

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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Toni T Seppälä, MD, PhD; Phone Number: +358444722846; Email: toni.seppala@tuni.fi

Study Locations

• Estonia
  • Tallin, Estonia
    • North Estonia Medical Centre
    • Contact: Indrek Seire, MD, PhD; Email: indrek.seire@ut.ee
  • Tallin, Estonia
    • West Tallinn Central Hospital
    • Contact: Kaur Liivak, MD, PhD; Email: kaur.liivak@keskhaigla.ee
  • Tallinn, Estonia
    • East Tallinn Central Hospital
  • Tartu, Estonia
    • Tartu University Hospital
    • Contact: Jaan Soplepman, MD, PhD; Email: jaan.soplepmann@kliinikum.ee
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Central Hospital
    • Contact: Anna H Lepistö, MD, PhD; Email: anna.lepisto@hus.fi
  • Joensuu, Finland
    • North Karelia Central Hospital
    • Contact: Markku Matikainen, MD, PhD; Email: markku.matikainen@siunsote.fi,
  • Jyväskylä, Finland
    • Jyväskylä Central Hospital
    • Contact: Kyösti Tahkola, MD, PhD; Email: kyosti.tahkola@hyvaks.fi
  • Kuopio, Finland
    • Kuopio University Hospital
    • Contact: Anne Fageström, MD, PhD; Email: anne.fagerstrom@pshyvinvointialue.fi
  • Oulu, Finland
    • Oulu University Hospital
    • Contact: Karoliina Paarmio, MD, PhD; Email: karoliina.paarnio@pohde.fi
  • Pori, Finland
    • Satakunta Central Hospital
    • Contact: Jyrki Haikonen, MD, PhD; Email: jyrki.haikonen@sata.fi
  • Seinäjoki, Finland
    • Seinäjoki Central Hospital
  • Tampere, Finland, 33400
    • Tampere University Hospital
    • Contact: Toni T Seppälä, MD, PhD; Phone Number: +358444722846; Email: toni.seppala@tuni.fi
  • Turku, Finland
    • Turku University Hospital
    • Contact: Pirita Varpe, MD, PhD; Email: Pirita.Varpe@tyks.fi

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nonoperative management; The patients presenting with complete clinical response undergo nonoperative management (i.e. watch & wait) as surveillance for local regrowth or distant spread.	Procedure: Nonoperative surveillance; Clinical and imaging surveillance with digital rectal examination and/or endoscopy, rectal MRI and body CT; Other Names: Watch and Wait; Organ preservation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Survival from complete clinical response to locoregional failure or distant metastases	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: Turku University Hospital; Helsinki University Central Hospital; Oulu University Hospital; Kuopio University Hospital; Seinajoki Central Hospital; Tampere University; Tartu University Hospital; Satakunta Central Hospital; Jyväskylä Central Hospital; North Karelia Central Hospital; North Estonia Medical Centre; East Tallinn Central Hospital; West Tallinn Central Hospital
• Investigators: Principal Investigator: Toni T Seppälä, MD, PhD, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: R24008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The European Data Protection Regulation (GDPR) does not allow sharing other than anonymised patient level data.

Drug and device information, study documents

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