Radiotherapy in IDH Mutated Glioma: Evaluation of Late Outcomes

NCT04304300 | Completed DMC

• 2 other identifiers: NL69780.078.19Netherlands Trial Register
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 5

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.

Conditions

Astrocytoma, Grade II; Astrocytoma, Grade III; Oligodendroglioma; Oligodendroglioma, Anaplastic

Outcome Measures

Primary Outcomes (2)

• Toxicity (selected CTCAE 5.0 items)

  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.

  24 months

• Neurocognitive testing

  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)

  24 months

Secondary Outcomes (5)

• Next intervention free survival (NIFS)

  48 months

• Progression Free Survival (PFS)

  48 months

• Overall Survival (OS)

  48 months

• Health Related Quality of Life (HRQOL)

  24 months

• Health - Related Economics

  24 months

Other Outcomes (1)

• Radiological data

  4 months

Study Arms (1)

Study group

Glioma, IDH mutated, grade 2 and 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Erasmus Medical Center: lead
• HollandPTC: collaborator
• Amsterdam University Medical Center: collaborator
• Leiden University Medical Center: collaborator
• Delft University of Technology: collaborator
• Medical Center Haaglanden: collaborator

Study Sites (5)

Erasmus MC

Rotterdam, South Holland, 3015 CE, Netherlands

Location

Amsterdam UMC

Amsterdam, 1081 HV, Netherlands

Location

HollandPTC

Delft, 2629 JH, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Haaglanden Medical Center

Leidschendam, 2262BA, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood, optional

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 11, 2020
• Study Start: December 10, 2019
• Primary Completion: June 15, 2024
• Study Completion: June 15, 2024
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (5)