Comparing Radical Surgery and Radical Radiotherapy as First Definitive Treatment for Primary MCC

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

Detailed Description
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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.

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

Conditions
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Merkel Cell Carcinoma

Intervention / Treatment
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* Radiation: Radiotherapy
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Inclusion Criteria for All Patients: Patients newly diagnosed with histologically-proven MCC (either primary and/or regional nodal disease) 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 No confirmed distant metastases beyond the regional nodal basin (i.e. not stage IV disease) Suitable for radical treatment to achieve disease control Able to give valid informed consent Consent for collection of data and tissue samples and follow up Life expectancy six months or greater in relation to general fitness and co-morbidities Additional Inclusion Criteria for Rational Compare: Patients newly diagnosed with histologically-proven primary MCC 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 A minimum margin of 1 cm surrounding the MCC achievable by either radiotherapy or surgery Consent for randomisation into Rational Compare Exclusion Criteria: The primary MCC has already been treated radically with WLE (surgical margins >10 mm) or radiotherapy Intended use of regional or systemic chemotherapy for MCC (including molecularly targeted agents and immunotherapy)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase III
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Prioritise Radiotherapy<br>Radical radiotherapy to macroscopic tumour and/or to the tumour bed if already excised, plus a wide margin. | Radiation: Radiotherapy<br>* Radiotherapy<br>|
| Experimental: Arm B: Prioritise Surgery<br>Wide Local Excision (WLE), aiming for complete excision of all MCC, plus a wide margin | Procedure: Surgery<br>* Surgery<br>|

What is the study measuring?
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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 |