Comparing Radical Surgery and Radical Radiotherapy as First Definitive Treatment for Primary MCC (Rational-MCC)

Rational-MCC: A Randomised Phase III Multi-centre Trial Comparing Radical Surgery and Radical Radiotherapy as First Definitive Treatment for Primary MCC

A randomised phase III multi-centre trial comparing radical surgery and radical radiotherapy as first definitive treatment for primary MCC

Study Overview

• Status: Completed
• Conditions: Merkel Cell Carcinoma
• Intervention / Treatment: Procedure: Surgery; Radiation: Radiotherapy

Detailed Description

A randomised phase III multi-centre trial comparing radical surgery and radical radiotherapy as first definitive treatment for primary MCC with an observational study for patients ineligible for the randomised trial.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • University Hospital Birmingham NHS Foundation Trust
  • Bristol, United Kingdom
    • North Bristol NHS Trust
  • Cambridge, United Kingdom
    • Cambridge University Hospitals NHS Foundation Trust
  • Dundee, United Kingdom
    • NHS Tayside
  • London, United Kingdom
    • Barts Health NHS Trust
  • Manchester, United Kingdom
    • Christie NHS Foundation Trust
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospitals Nhs Foundation Trust
  • Nottingham, United Kingdom
    • Nottingham University Hospitals NHS Trust
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Trust
  • Prescot, United Kingdom
    • St Helens and Knowsley Hospitals NHS Trust
  • Preston, United Kingdom
    • Lancashire Teaching Hospitals NHS Foundation Trust
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals NHS Foundation Trust
  • Stoke-on-Trent, United Kingdom
    • University Hospital of North Midlands Trust
  • Truro, United Kingdom
    • Royal Cornwall Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

General Inclusion Criteria for All Patients:

1. Patients newly diagnosed with histologically-proven MCC (either primary and/or regional nodal disease)
2. Completion of clinical and radiological staging investigations, including CT imaging (or other modality) of regional nodal basin(s) and major viscera (and SLNB if clinically appropriate) to identify regional and distant metastases
3. No confirmed distant metastases beyond the regional nodal basin (i.e. not stage IV disease)
4. Suitable for radical treatment to achieve disease control
5. Able to give valid informed consent
6. Consent for collection of data and tissue samples and follow up
7. Life expectancy six months or greater in relation to general fitness and co-morbidities

Additional Inclusion Criteria for Rational Compare:

1. Patients newly diagnosed with histologically-proven primary MCC
2. In the opinion of the SSMDT, the primary MCC can be encompassed both within a wide surgical margin and within a radiotherapy field, and the SSMDT is in equipoise regarding WLE or radiotherapy as first treatment
3. A minimum margin of 1 cm surrounding the MCC achievable by either radiotherapy or surgery
4. Consent for randomisation into Rational Compare

Exclusion Criteria:

1. The primary MCC has already been treated radically with WLE (surgical margins >10 mm) or radiotherapy
2. Intended use of regional or systemic chemotherapy for MCC (including molecularly targeted agents and immunotherapy)

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: Arm A: Prioritise Radiotherapy; Radical radiotherapy to macroscopic tumour and/or to the tumour bed if already excised, plus a wide margin.	Radiation: Radiotherapy; Radiotherapy
Experimental: Arm B: Prioritise Surgery; Wide Local Excision (WLE), aiming for complete excision of all MCC, plus a wide margin	Procedure: Surgery; Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to loco-regional failure	The time to loco regional failure for all patients is the time from randomisation to loco-regional treatment failure	Time from randomisation to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients alive and free of loco-regional disease	(irrespective of whether loco-regional failure has been previously demonstrated)	Time from randomisation to 3 years
Time to 'local failure'-the time from randomisation to macroscopic persistence, progression or recurrence between the primary site and regional nodal basin(s)	(including in-field and in transit metastases)	Time from randomisation to 3 years
Time to regional nodal failure	Time to regional nodal failure	Time from randomisation to 3 years
Time to distant progression	Time to distant progression	Time from randomisation to 3 years
Patient Progression free survival	Patient Progression free survival	Time from randomisation to 3 years
Patient survival	Survival from randomisation	Time from randomisation to 3 years
Quality of life assessed by questionnaires	Quality of life assessed by QLQC30/ EQ-5L-5D questionnaire completion	Time from randomisation to 3 years

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: Efficacy and Mechanism Evaluation (EME) Programme
• Investigators: Principal Investigator: Neil Steven, University of Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2016
• Primary Completion (Actual): January 22, 2022
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma, Merkel Cell
• Other Study ID Numbers: RG_14-019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No