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Radiotherapy in IDH Mutated Glioma: Evaluation of Late Outcomes (RIGEL)

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ClinicalTrials.gov Identifier: NCT04304300
Recruitment Status : Recruiting
First Posted : March 11, 2020
Last Update Posted : March 25, 2020
Sponsor:
Collaborators:
HollandPTC
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Leiden University Medical Center
Delft University of Technology
Medical Center Haaglanden
Information provided by (Responsible Party):
Alejandra Mendez Romero, Erasmus Medical Center

Brief Summary:

Rationale: Standard postoperative treatment of isocitrate dehydrogenase 1/2 mutated grade 2 and 3 glioma (IDHmG) consists of radiotherapy and chemotherapy. The improving prognosis of these patients leads towards more emphasis on the long-term effects of treatment. Specifically radiotherapy has been implicated in the development of delayed neurocognitive deterioration. The impact of modern radiotherapy techniques (such as intensity modulated radiotherapy, volumetric modulated radiotherapy and proton beam therapy) and chemotherapy on general toxicity, late neurocognitive outcomes and imaging changes is currently unclear.

Objectives:

  • To report treatment outcomes and radiation-induced toxicity from a prospective, multicentre observational cohort of IDHmG patients treated with radiotherapy and chemotherapy,
  • To integrate radiotherapeutic dose distributions, imaging changes and neuropsychological outcome in IDHmG.
  • To evaluate the Dutch selection criteria for proton therapy applied to IDHmG based on the outcomes collected in this observational study.
  • To assess the impact of proton and photon therapy on health-related quality of life (HRQoL) and health-related economics (HR-E) in IDHmG patients.
  • To collect genetic material for future translational research into the interaction between germline DNA, prognosis and radiation-induced toxicity.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This project is a multicentre, observational cohort of patients undergoing radiotherapy and chemotherapy for IDHmG. The protocol closely follows the local guidelines for clinical follow-up. Specific to the study are extra questionnaires and specific imaging acquired during scheduled MRI's. Routine neuropsychological investigation is standard of care in Erasmus Medical Center (Erasmus MC), but not in all participating centers. We feel the additional burden of participation in this study to be low.


Condition or disease
Astrocytoma, Grade II Astrocytoma, Grade III Oligodendroglioma Oligodendroglioma, Anaplastic

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Study Type : Observational
Estimated Enrollment : 79 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Radiotherapy in IDH Mutated Glioma: Evaluation of Late Outcomes
Actual Study Start Date : December 10, 2019
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine


Group/Cohort
Study group
Glioma, IDH mutated, grade 2 and 3



Primary Outcome Measures :
  1. Toxicity (selected CTCAE 5.0 items) [ Time Frame: 24 months ]
    The Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 displays Grade 1 to 5, ranging from 'mild' to 'death'. The case report form will include a predefined set of CTCAE items of expected radiotherapy related toxicities. In addition, other CTCAE toxicities grade ≥ 2 that are likely, possibly or definitely related to the radiotherapy should be recorded in the case report form (CRF), when they occur. All items will include a causality assessment: likely or definitely attributable to radiotherapy, unrelated or unlikely attributable to radiotherapy, or not assessable.

  2. Neurocognitive testing [ Time Frame: 24 months ]
    Neurocognitive functioning will be assessed with a standard and well established short neuropsychological test battery, developed for use in clinical trials. The following tests are included: Hopkins Verbal Learning Test (HVLT), Trail Making Test part A and B (TMT A/B), Controlled Oral Word Association (COWA), Medical Outcomes Study Cognitive Functioning Scale (MOS), Diagnostic Instrument for Mild Aphasia (DIMA)


Secondary Outcome Measures :
  1. Next intervention free survival (NIFS) [ Time Frame: 48 months ]
    NIFS is defined as time from first irradiation to date of initiation of further treatment after radio- and/or chemotherapy or death (any cause), whichever occurs first.

  2. Progression Free Survival (PFS) [ Time Frame: 48 months ]
    PFS is defined as the time from first irradiation to progressive disease, according to (any of) the Response Asessment in Neuro Oncology (RANO) criteria for progressive disease in low grade glioma.

  3. Overall Survival (OS) [ Time Frame: 48 months ]
    OS is defined as time from first irradiation to date of death from any cause.

  4. Health Related Quality of Life (HRQOL) [ Time Frame: 24 months ]
    HRQoL will be assessed with the EORTC quality of life questionnaire (QLQ-C30) supplemented by the neuro-oncological module (QLQ-BN20) and the Euro Quality of Life questionnaire (EQ5D-5L)

  5. Health - Related Economics [ Time Frame: 24 months ]
    For the Health Related Economics (HR-E) analyses, the EQ5D - 5L questionnaire will be used in conjunction with the Productivity Costs Questionnaire (iPCQ) and the Medical Consumption Questionnaire (iMCQ). These questionaires are optional.


Other Outcome Measures:
  1. Radiological data [ Time Frame: 4 months ]
    If feasible, pre- and 4 months post-treatment a scan protocol will be used that, besides the standard clinical imaging, will focus on (micro-)structural and microvascular characteristics that could predict neurocognitive outcome and treatment efficacy. This feasibility is site-specific.


Biospecimen Retention:   Samples With DNA
blood, optional


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
IDH mutated glioma patients, WHO grade 2 and 3, who undergo postoperative radiotherapy and chemotherapy as standard treatment.
Criteria

Inclusion Criteria:

  • Histologically confirmed glioma, World Health Organisation (WHO) grade 2 or 3, IDH mutated
  • Indication for standard treatment with radiotherapy and chemotherapy. For WHO grade 2 tumors 50.4 Gy relative biological equivalent (RBE) in 28 fractions. For WHO grade 3 tumors 59.4 Gy (RBE) in 33 fractions.
  • Ability to comply with the protocol, including neuropsychological testing and imaging.
  • Ability to understand the requirements of the study and to give written informed consent, as determined by the treating physician.
  • Written informed consent.

Exclusion Criteria:

  • Any prior chemotherapy for IDHmG. This includes upfront postoperative chemotherapy.
  • Any prior cranial radiotherapy, including but not limited to radiotherapy for IDHmG.
  • Prior invasive malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with current prostate specific antigen (PSA) of less than or equal to 0.1 ng/mL).
  • Extensive white matter disease visible on pre-therapy imaging (Fazekas grade ≥2)
  • Contra-indication for magnetic resonance (MR) imaging (i.e. metal implants, claustrophobia)
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule in the participating hospitals
  • Any other serious medical condition that could interfere with follow-up.
  • Severe aphasia or language barrier interfering with assessing endpoints (i.e. completion of questionnaires or neurocognitive performance)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04304300


Contacts
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Contact: Jaap Jaspers, MD 107042982 ext +31 j.jaspers@erasmusmc.nl

Locations
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Netherlands
Erasmus MC Recruiting
Rotterdam, Zuid Holland, Netherlands, 3015 CE
Contact: Alejandra Mendez Romero, MD PhD    +31 (0)10 7035829    a.mendezromero@erasmusmc.nl   
Principal Investigator: Alejandra Mendez Romero, MD, PhD         
Amsterdam UMC Not yet recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Frank Lagerwaard, MD, PhD    20 4440436 ext +31    fj.lagerwaard@vumc.nl   
HollandPTC Recruiting
Delft, Netherlands, 2629 JH
Contact: Marco van Vulpen, Prof. MD    88 5018800 ext +31    m.van.vulpen@hollandptc.nl   
Leiden University Medical Center Not yet recruiting
Leiden, Netherlands, 2333 ZA
Contact: Ida Coremans, MD, PhD    071 5263525    i.e.m.coremans@lumc.nl   
Haaglanden Medical Center Not yet recruiting
Leidschendam, Netherlands, 2262BA
Contact: Ruud Wiggenraad, MD, PhD    88 979 2071 ext +31    r.wiggenraad@haaglandenmc.nl   
Sponsors and Collaborators
Erasmus Medical Center
HollandPTC
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Leiden University Medical Center
Delft University of Technology
Medical Center Haaglanden
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Responsible Party: Alejandra Mendez Romero, MD, PhD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT04304300    
Other Study ID Numbers: NL69780.078.19
Netherlands Trial Register ( Registry Identifier: NL7993 )
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Astrocytoma
Oligodendroglioma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue