Astrocytoma, Grade IIRIGELNCT04304300
Radiotherapy in IDH Mutated Glioma: Evaluation of Late Outcomes
An observational study of Astrocytoma, Grade II and Astrocytoma, Grade III, run by Erasmus Medical Center at 5 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Astrocytoma, Grade II, Astrocytoma, Grade III, Oligodendroglioma
- How many people
- 80 participants
- Where
- 5 sitesNetherlands
- Study dates
- 10 Dec 2019to 15 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: IDH mutated glioma patients, WHO grade 2 and 3, who undergo postoperative radiotherapy and chemotherapy as standard treatment.
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites
Amsterdam UMC
Amsterdam, 1081 HV
HollandPTC
Delft, 2629 JH
Leiden University Medical Center
Leiden, 2333 ZA
Haaglanden Medical Center
Leidschendam, 2262BA
Erasmus MC
Rotterdam, South Holland, 3015 CE
About this study
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:
Read more
- 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
- Medical subject headings
- Astrocytoma, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Study group | Glioma, IDH mutated, grade 2 and 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 24 months
Secondary outcomes (5)
Next intervention free survival (NIFS)
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.
Measured: 48 months
Progression Free Survival (PFS)
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.
Measured: 48 months
Overall Survival (OS)
OS is defined as time from first irradiation to date of death from any cause.
Measured: 48 months
Health Related Quality of Life (HRQOL)
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)
Measured: 24 months
Health - Related Economics
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2020
- Study start10 Dec 2019
- Primary completion15 Jun 2024
- Study completion15 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Astrocytoma, Grade IIStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- HollandPTC, Amsterdam University Medical Center, Leiden University Medical Center, Delft University of Technology, Medical Center Haaglanden
- Responsible party
- Principal investigator, Alejandra Mendez Romero, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04304300
- Sponsor's protocol ID
- NL69780.078.19
- Other IDs
- Netherlands Trial Register
- Acronym
- RIGEL
- Status last verified
- Oct 2024
- First submitted
- 9 Mar 2020
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiotherapy in IDH Mutated Glioma: Evaluation of Late Outcomes
- ClinicalTrials.gov ID
- NCT04304300
- Acronym / sponsor ID
- RIGEL / NL69780.078.19
- Conditions
- Astrocytoma, Grade II, Astrocytoma, Grade III, Oligodendroglioma, Oligodendroglioma, Anaplastic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- HollandPTC, Amsterdam University Medical Center, Leiden University Medical Center, Delft University of Technology, Medical Center Haaglanden
- Study start
- 10 Dec 2019 (actual)
- Primary completion
- 15 Jun 2024 (actual)
- Study completion
- 15 Jun 2024 (actual)
- First posted
- 11 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study group | – | –Glioma, IDH mutated, grade 2 and 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- IDH mutated glioma patients, WHO grade 2 and 3, who undergo postoperative radiotherapy and chemotherapy as standard treatment.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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)
5 secondary outcomes
Next intervention free survival (NIFS)
Time frame: 48 months
Progression Free Survival (PFS)
Time frame: 48 months
Overall Survival (OS)
Time frame: 48 months
Health Related Quality of Life (HRQOL)
Time frame: 24 months
Health - Related Economics
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Astrocytoma, Grade II and Astrocytoma, Grade III, run by Erasmus Medical Center at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity (selected CTCAE 5.0 items) (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.