Early Therapy Response Monitoring in Melanoma Patients Using PET/MRI

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

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.

Study Overview

• Status: Unknown
• Conditions: Malignant Melanoma Stage IV
• Intervention / Treatment: Diagnostic test: PET/MR (Biograph mMR)

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nina Schwenzer, MD; Phone Number: +49 7071 29-87720; Email: nina.schwenzer@uni-tuebingen.de

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • Recruiting
    • Dept. of Radiology, University of Tuebingen
    • Contact: Christina Pfannenberg, MD; Phone Number: +49 7071 2982756; Email: christina.pfannenberg@med.uni-tuebingen.de
    • Contact: Brigitte Gueckel; Phone Number: +49 7071 2981212; Email: brigitte.gueckel@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Publications and helpful links

General Publications

• Seith F, Forschner A, Weide B, Guckel B, Schwartz M, Schwenck J, Othman AE, Fenchel M, Garbe C, Nikolaou K, Schwenzer N, la Fougere C, Pfannenberg C. Is there a link between very early changes of primary and secondary lymphoid organs in 18F-FDG-PET/MRI and treatment response to checkpoint inhibitor therapy? J Immunother Cancer. 2020 Aug;8(2):e000656. doi: 10.1136/jitc-2020-000656. Erratum In: J Immunother Cancer. 2020 Sep;8(2):

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2014
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: GK-MR/PET Tü-004

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