Early Therapy Response Monitoring in Melanoma Patients Using PET/MRI

Study Overview
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Brief Summary
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Therapeutic agents used in malignant melanoma treatment such as BRAF/MEK inhibitors and anti-CTLA-4/Anti-PD-1 antibodies go along with harmful side effects in a considerable proportion of patients and treatment costs may cause relevant medical expenditures per month. Currently, therapy response assessment in melanoma patients is performed using RECIST criteria which are based on changes in tumour size. PET/CT combines morphological and metabolic information. Thus, the so-called PERCIST-criteria were introduced integrating change in size and glucose utilization for response assessment in solid tumors. Due to the different mechanism of action these new agents introduce different response patterns increase in tumor size due to inflammation for antibody therapies). In conventional chemotherapies, re-staging is usually performed 3 months after treatment initiation which is the result of empirical investigations. Moreover, it has recently been shown, that response to new targeted therapies can be detected much earlier using PET or functional MR techniques. This forms the rationale for the monitoring of melanoma patients using a combined PET/MR technique after only 2 weeks of therapy initiation. Especially for patients in stage IV with a medium survival time of 12 months, a 2.5 months earlier re-staging and therapy adjustment would have significant consequences for the individual clinical course.

Official Title
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Early Response Monitoring of Systemic Therapies in Patients With Advanced Melanoma by Simultaneous Positron-emission-tomography (PET)/Magnetic Resonance Imaging (MRI)

Conditions
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Malignant Melanoma Stage IV

Intervention / Treatment
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* Diagnostic Test: PET/MR (Biograph mMR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient with diagnosed unresectable malignant melanoma stage IV age: ≥18 years planned systemic therapy with either new therapies (BRAF/MEK inhibitors, Anti-CTLA-4/Anti-PD-1 antibodies) or conventional chemotherapeutics (CTx) clinically indicated routine PET/CT (baseline t0) demonstrating at least one measurable lesion PET/CT for baseline-staging and therapy monitoring (clinical indication required) informed consent Exclusion Criteria: contraindications for MR-imaging (metal implants, claustrophobia, etc.) contraindications for gadolinium-based contrast agent acute infections or other acute diseases pregnant or breast-feeding women disability for informed consent

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: PET/MR (Biograph mMR)|The combination of PET and MRI allows for evaluation of metabolic, functional and morphological parameters such as glucose metabolism, perfusion, diffusion restriction or size in one examination. Due to the combination of MRI and PET in one scanner it is possible to align the acquired PET and MR datasets with high precision|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early therapy response assessment | Early therapy response assessment by multiparametric hybrid imaging (PET/MRI) two weeks (early time point - study visit) and three months (regular staging) after therapy initiation with regard to optimizing patient management (please note: no therapy change intended based on the imaging at early time point (study visit t1)). Early study imaging data and later regular imaging data have to be compared. | Baseline t0 (1st imaging / start of therapy), early therapy response (study visit) t1 (2 weeks after therapy start), regular therapy response (routine visit) t2 (3 month after therapy start) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prognostic capacity of morphological and functional MRI measures | testing the prognostic capacity of morphological and functional MRI measures (diffusion, perfusion) for predicting the concordance of therapy response results two weeks and three months after treatment initiation | 3 month | 
| prognostic value of PET/MRI-specific response | validation of the significance and prognostic value of the defined PET/MRI-specific response evaluation criteria by correlation with TTP | 18 month |