Early evaluation of therapy response (targeted therapy and immunotherapy) in patients with metastasized malignant melanoma by multiparametric PET/MR imaging.
Organizational Data
- DRKS-ID:
- DRKS00013925
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2018-01-29
- Last update in DRKS:
- 2023-06-23
- Registration type:
- Retrospective
Acronym/abbreviation of the study
GK-MR/PET Tü-004
URL of the study
No Entry
Brief summary in lay language
Standard therapy response assessment of malignant melanoma (Stage IV) patients did not respect different modes of action of new therapies such as antibodies. In particular imaging of immune responses to tumors is difficult. New molecular imaging methods may solve this problem. They are able to indicate different tumor characteristics during one examination step. Depending on individual tumor characteristics they may respond either rather quickly or not at all to immunotherapy. Thus, it should be possible to differentiate rather quickly between responding and non-responding patients. The aim of the study is to evaluate if combined positronemission/magnetic resonance tomography (PET/MR) has the potential to detect responders already two weeks after immunotherapy initiation. A very early re-staging and therapy adjustment would have significant consequences for the individual clinical course: in case of non-responders an early switch to a maybe more effective therapy as well as the prevention of side-effects by noneffective therapies. The aim of the trial is to test multiparametric PET/MR imaging for early therapy response assessment at an early time point (two weeks after treatment initiation) in comparison to the regular response interval after twelve weeks in melanoma patients (without therapy modification).
Brief summary in scientific language
BRAF/MEK inhibitors and anti-CTLA-4/Anti-PD-1 antibodies in melanoma treatment go frequently along with harmful side effects. Treatment costs may cause relevant medical expenditures per month. Currently, therapy response assessment 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. These new agents introduce different response patterns. 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.
Health condition or problem studied
- ICD10:
- C43.9 - Malignant melanoma of skin, unspecified
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- PET/MR examination of melanoma patients (Stage IV) at timepoints of therapy initiation (t0), as well as 2 weeks (t1) and 12 weeks (t2) after therapy start.
Endpoints
- Primary outcome:
- Comparison of patient's treatment response rate as assessed by PET/MRI acquired two weeks and three months after therapy initiation using standard response criteria (RECIST, PERCIST).
- Secondary outcome:
- -Testing the prognostic capacity of morphological and functional MR measures (diffusion, perfusion) for predicting the concordance of therapy response results two weeks and three months after treatment initiation. -Definition of PET/MRI-specific criteria for therapy response evaluation with respect to the personalized treatment approach, e.g. mode of action of “biologicals” (kinase inhibitor and therapeutical antibodies). -Validation of the significance and prognostic value of the defined PET/MRI-specific response evaluation criteria by correlation with TTP and OS.
Study Design
- Purpose:
- Diagnostic
- Allocation:
- N/A (single arm study)
- Control:
-
- Uncontrolled/single arm
- Phase:
- N/A
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Single (group)
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Radiologische Klinik und Hautklinik Tübingen
Recruitment period and number of participants
- Planned study start date:
- No Entry
- Actual study start date:
- 2014-09-29
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2019-09-03
- Target Sample Size:
- 70
- Final Sample Size:
- 62
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- 99 Years
- Additional Inclusion Criteria:
- -Patient with diagnosed unresectable malignant melanoma stage IV, -Age: ≥18 years, -Planned systemic therapy with new therapies: BRAF/MEK inhibitors, Anti-CTLA-4/Anti-PD-1 antibodies, -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
Addresses
Primary Sponsor
- Address:
- Universitätsklinikum Tübingen, Radiologische Klinik, Diagnostische & Interventionelle RadiologieProf. Dr. med. Christina PfannenbergHoppe-Seyler-Str. 372076 TübingenGermany
- Telephone:
- 07071-29-82756
- Fax:
- 07071-29-4548
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.med.uni-tuebingen.de/Forschung/Kliniken/Radiologie.html
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum Tübingen, Radiologische Klinik, Diagnostische & Interventionelle RadiologieDr. med. Ferdinand SeithHoppe-Seyler-Str. 372076 TübingenGermany
- Telephone:
- 07071-29-68627
- Fax:
- 07071-29-4548
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.med.uni-tuebingen.de/Forschung/Kliniken/Radiologie.html
Contact for Public Queries
- Address:
- Universitätsklinikum Tübingen, Hautklinik, Sektion für Dermatologische OnkologieProf. Dr. med. Thomas EigentlerLiebermeisterstr. 272076 TübingenGermany
- Telephone:
- 07071-29-85748
- Fax:
- 07071-29-5187
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://hautklinik-tuebingen.de/
Principal Investigator
- Address:
- Universitätsklinikum Tübingen, Radiologische Klinik, Diagnostische & Interventionelle RadiologieDr. med. Ferdinand SeithHoppe-Seyler-Str. 372076 TübingenGermany
- Telephone:
- 07071-29-68627
- Fax:
- 07071-29-4548
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.med.uni-tuebingen.de/Forschung/Kliniken/Radiologie.html
Sources of Monetary or Material Support
Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)
- Address:
- Wilhelm Sander StiftungGoethestr. 7480336 MünchenGermany
- Telephone:
- 089 544187-0
- Fax:
- 089 544187-20
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.sanst.de
Institutional budget, no external funding (budget of sponsor/PI)
- Address:
- Universitätsklinikum TübingenGeissweg 372076 TübingenGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.medizin.uni-tuebingen.de
Ethics Committee
Address Ethics Committee
- Address:
- Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum TübingenGartenstr. 4772074 TübingenGermany
- Telephone:
- +49-7071-2977661
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.medizin.uni-tuebingen.de/de/medizinische-fakultaet/ethikkommission
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2012-05-21
- Ethics committee number:
- 251/2012BO1
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2012-08-23
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- Seith et al: 18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start. Eur J Nucl Med Mol Imaging. 2018 Jan;45(1):95-101. Immunother Cancer 2020;8:e000656. doi:10.1136/jitc-2020-000656
- Seith et al: Is there a link between very earlychanges of primary and secondary lymphoid organs in 18F-FDG-PET/MRIand treatment response to checkpointinhibitor therapy? J Immunother Cancer 2020;8:e000656. doi:10.1136/jitc-2020-000656
- Küstner et al. Development of a Hybrid-Imaging-Based Prognostic Index forMetastasized-Melanoma Patients in Whole-Body 18F-FDGPET/CT and PET/MRI Data. Diagnostics 2022, 12, 2102. https://doi.org/10.3390/diagnostics12092102
- Date of first publication of study results:
- 2017-08-22
- DRKS entry published for the first time with results:
- 2018-08-03
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry