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Completed

NCT Number: NCT04304300

Radiotherapy in IDH Mutated Glioma: Evaluation of Late Outcomes

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.

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Key information

Conditions

Astrocytoma, Grade II Astrocytoma Astrocytoma, Grade III Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Oligodendroglioma Oligodendroglioma, Anaplastic

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Erasmus MC, Rotterdam, South Holland, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Primary outcomes

  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 outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Erasmus Medical Center

Other

Collaborators

  • Amsterdam University Medical Center
  • Delft University of Technology
  • HollandPTC
  • Leiden University Medical Center
  • Medical Center Haaglanden

Registry information

Acronym: RIGEL

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
Mar 11, 2020
Registry last updated
Oct 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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