Merkel Positron Emission Tomography (PET) Protocol

Study Overview
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Brief Summary
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A Phase II Study designed to evaluate the efficacy of Chemo-Radiotherapy in achieving loco-regional control in patients with Merkel Cell Carcinoma (MCC) of the skin. Patients will undergo PET scans to assist in staging and planning the patient's treatment as well as assessing response at the conclusion of treatment.

Official Title
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A Phase II Efficacy Study of Chemo-Radiotherapy in PET Stage II and III Merkel Cell Carcinoma of the Skin

Conditions
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Merkel Cell Carcinoma

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Etoposide
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Trial Registration: Patients may be registered on the trial only if they meet all of the following criteria: Age 18 years or older Written informed consent to participate in the study Able to undergo 18-FDG PET scan (no uncontrolled diabetes mellitus or severe claustrophobia). Available for follow-up. Using adequate contraception if capable of child bearing Any Merkel Cell carcinoma confined to the primary and/or nodal sites ECOG 0-2. Full Blood Count (FBC) should be satisfactory ( Haemoglobin > or equal to 10g/dl, neutrophils > or equal to 2.0 x 109 /l and platelets > or equal to 100 x 109 /l) and renal function (GFR > or equal to 50 ml/min) and hepatic function ( ALT < 5 X upper limit normal, bilirubin < 1.5 X upper limit normal) Patients must be able to tolerate protocol treatment Exclusion Criteria for Registration: Previous chemotherapy in the past 5 years or prior radiotherapy to the area of concern Unable to comply with treatment protocol eg dementia Other malignancy in the past 5 years other than non-melanoma skin cancer. Women who are pregnant or lactating. Clinical evidence of metastatic disease. Immunosuppression from long term steroid use or immunosuppressive drugs. Any serious illness or medical condition that precludes the safe administration of the chemotherapy including: Active infection Uncontrolled or unstable cardiac disease including unstable angina, myocardial infarction within the last 3 months, and recurrent ventricular arrhythmias Inclusion Criteria for Treatment Registration: Patients may proceed to protocol treatment if they meet the following criteria: High risk disease with no evidence of distant spread: Biopsy proven MCC with a primary that is > 2cm (T2N0M0= Stage II) and/or regional nodes (any T, N1M0= Stage III); OR Recurrent MCC not previously treated with radiation treatment; Dermal or in-transit metastasis with or without nodes; Occult primary with involved nodes Patients who have no metastases on CT or PET scan OR If CT is suggestive of metastases, they must be PET negative

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Conventional radical radiotherapy in this trial means that those patients with microscopic disease receive a dose of 50Gy using daily incremental fractions of 2Gy over 25 fractions and those with macroscopic disease receive 54Gy in 27 fractions. | Drug: Carboplatin<br>* During radiotherapy: Carboplatin (AUC2) commences on day 1 of radiation and is repeated at weekly intervals on days 8, 15, 22 and 29 (of radiation). After radiotherapy: 3 weeks after completing radiotherapy, 3 cycles of 3 weekly carboplatin (AUC4.5) intravenously on day 1.<br>Drug: Etoposide<br>* After Radiotherapy: 3 weeks after completing the radiation therapy, 3 cycles of 3 weekly etoposide (80mg/M2/day) intravenously days 1-3<br>Radiation: Radiotherapy<br>* Microscopic Disease: 50Gy delivered in 2Gy doses over 25 fractions Macroscopic Disease: 54Gy delivered in 2Gy doses over 27 fractions<br>* Other names: Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to loco-regional failure curve |  | Minimum of 18 months follow up | 
| Incidence of grade 3 and 4 toxicity and incidence of febrile neutropenia |  | Duration of Radiotherapy treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival and time to distant failure curves |  | 3 year acturarial curves | 
| Proportion of patients for which PET can influence management. |  | 12 weeks post Radiotherapy | 
| Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of PET. |  | 12 weeks post Radiotherapy | 
| Post-treatment PET complete response rate for patients with unresected disease |  | 12 weeks post Radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Merkel Cell Cancer, PET scanning