Low Grade GliomaPhase 2INDIGONCT05964569
Feasibility of Individualized, Model-guided Optimization of Proton Beam Treatment Planning in Patients With Low Grade Glioma
A Phase 2 study testing model-guided optimization of treatment plan and standard treatment plan, no optimization in people with Low Grade Glioma, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
Low-grade glioma (LGG) represent typically slowly growing primary brain tumors with world health organization (WHO) grade I or II who affect young adults around their fourth decade. Radiological feature on MRI is a predominantly T2 hyperintense signal, LGG show typically no contrast uptake. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low Grade Glioma
- What is being tested?
- model-guided optimization of treatment plan and standard treatment plan, no optimization
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteGermany
- Study dates
- 11 Nov 2023to 11 Nov 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Age > 18 years
- histologically proven low-grade glioma
- indication for definitive or adjuvant radiotherapy
- ability to understand character and personal consequences of the clinical trial
- written informed consent
Who cannot join
- previous cerebral irradiation
- contraindication for contrast-enhanced MRI
- neurofibromatosis
- participation in another clinical trial with competing objectives
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Adriane Lentz-Hommertgen, Phd contact
Germany1 site, 1 recruiting
- Recruiting
Department of Radiotherapy, University of Heidelberg
Heidelberg, 69120
Juergen Debus, Prof. Dr. Dr., +49 6221 56 ext. 8200, juergen.debus@med.uni-heidelberg.de
Adriane Hommertgen, Dr. med., 0622156 ext. 34091, adriane.hommertgen@med.uni-heidelberg.de
About this study
Official title: Prospective Phase II Trial to Assess Feasibility of Individualized, Model-guided Optimization of Proton Beam Treatment Planning in Patients With Low Grade Glioma Multicentric, Prospective Interventional, Randomized, Observer Blind Two Arm (Active Control), Parallel Group Investigator-initiated Phase II Trial
Low-grade glioma (LGG) represent typically slowly growing primary brain tumors with world health organization (WHO) grade I or II who affect young adults around their fourth decade. Radiological feature on MRI is a predominantly T2 hyperintense signal, LGG show typically no contrast uptake. Radiotherapy plays an important role in the treatment of LGG. However, not least because of the good prognosis with long term survivorship the timing of radiotherapy has been discussed controversially. In order to avoid long term sequelae such as neurocognitive impairment, malignant transformation or secondary neoplasms initiation was often postponed as long as possible
Read the detailed description
Since patients with low grade glioma are expected to become long-term survivors, the prevention of long-term sequelae is particularly important. In addition to disease progression, also treatment related side effects such as decline of neurocognitive function, endocrine impairment or sensorineural deficits can have a negative impact on patient's quality of life.
Owing to the biophysical properties of protons with an inverse depth dose profile compared to photons and a steep dose fall of to the normal tissue, there is a strong rationale for the use of PRT in the treatment of patients with low-grade glioma. Although data from large randomized trials are still missing there is increasing evidence from smaller prospective trials and retrospective analyses that the expected advantages indeed transform into clinical advantages.
However, in about 20 % of all patients, late contrast-enhancing brain lesions (CEBL) appear on follow-up MR images 6 - 24 months after treatment. At HIT in Heidelberg and at OncoRay in Dresden, CEBLs have been observed to occur at very distinct locations in the brain and relative to the treatment field. Retrospective analysis has elucidated potential key factors that lead to CEBL occurrence. However, avoidance of CEBLs is hardly feasible using conventional treatment planning strategies. Model-aided risk avoidance denotes the use of model-based CEBL risk calculations as an auxiliary tool for clinical treatment planning: Model-based risk calculations and risk reduction via software-based optimization help the clinician to minimize risk of CEBL occurrence during treatment planning.
- Conditions
- Low Grade Glioma
- Being tested
- model-guided optimization of treatment plan, standard treatment plan, no optimization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
model-guided optimization of treatment planOther
original treatmant plans are optimized based on model-based NTCP
standard treatment plan, no optimizationOther
original treatment plans are not optimized
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment plan | Active comparator | Model-based NTCP is calculated after plan approval, however, no further adjustments are to be made to the approved treatment plan Receives: Other: standard treatment plan, no optimization |
| Optimized treatment plan | Experimental | Allocated to Control Calculation of normal tissue complication probability (NTCP) Model-guided replanning. Replanning is performed with Raysearch Raystation. Optimizations objectives are:
1. the optimization objectives that control the maximum dose in the target volume employ a variable, LETd-dependent model for RBE that allows us to include the RBE-variations predicted by the NTCP model
2. the periventricular volume, defined as the volume closer than 4 mm to the ventricular wall, is included into the optimization with a constraint on its Equivalent Uniform Dose (EUD) and with the variable RBE model described above. Thereby, the combined effect of the RBE variation and increased sensitivity of the periventricular volume, as predicted by the NTCP model, is included.
The effectiveness of the re-planning is verified by a second NTCP computation. Receives: Other: model-guided optimization of treatment plan |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of contrast enhancing brain leasions
the cumulative incidence of contrast enhancing brain lesions
Measured: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain
Secondary outcomes (6)
radiation-induced brain injuries
incidence of radiation-induced brain injuries > CTC°II
Measured: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain
progression-free survival
number of surviving patients without tumor progression
Measured: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain
overall survival
number of surviving patients
Measured: observed within 24 months after Proton Beam Therapy (PRT) measured by quarterly contrast enhanced MRI of the brain
patient reported outcome
patient reported outcome according to points on the PRO-CTCAE questionaire, scored 0/1 for absent/present)
Measured: up to 24 months after completion of radiotherapy
quality of life QLQ-C30
scores on the QLQ-C30 questionare, scored 0 (absence) to 5 (fully present)
Measured: up to 24 months after completion of PRT
quality of life QLQ-BN20
scores on the QLQ-BN20 questionare, scored 0 (absence) to 5 (fully present)
Measured: up to 24 months after completion of PRT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2023
- Study start11 Nov 2023
- Primary completion11 Nov 2026 (estimated)
- Study completion11 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Low Grade GliomaStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, observer blind two arm (active control), parallel group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juergen Debus, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05964569
- Sponsor's protocol ID
- RadOnk-Indigo
- Acronym
- INDIGO
- Status last verified
- Jan 2024
- First submitted
- 19 Jul 2023
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sallem H, Harrabi S, Traneus E, Herfarth K, Debus J, Bauer J. A model-based risk-minimizing proton treatment planning concept for brain injury prevention in low-grade glioma patients. Radiother Oncol. 2024 Dec;201:110579. doi: 10.1016/j.radonc.2024.110579. Epub 2024 Oct 10.
PubMed 39393467
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Phase II Trial to Assess Feasibility of Individualized, Model-guided Optimization of Proton Beam Treatment Planning in Patients With Low Grade Glioma Multicentric, Prospective Interventional, Randomized, Observer Blind Two Arm (Active Control), Parallel Group Investigator-initiated Phase II Trial
- ClinicalTrials.gov ID
- NCT05964569
- Acronym / sponsor ID
- INDIGO / RadOnk-Indigo
- Conditions
- Low Grade Glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- 11 Nov 2023 (actual)
- Primary completion
- 11 Nov 2026 (estimated)
- Study completion
- 11 Nov 2028 (estimated)
- First posted
- 28 Jul 2023 (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.
Low-grade glioma (LGG) represent typically slowly growing primary brain tumors with world health organization (WHO) grade I or II who affect young adults around their fourth decade. Radiological feature on MRI is a predominantly T2 hyperintense signal, LGG show typically no contrast uptake. Radiotherapy plays an important role in the treatment of LGG. However, not least because of the good prognosis with long term survivorship the timing of radiotherapy has been discussed controversially. In order to avoid long term sequelae such as neurocognitive impairment, malignant transformation or secondary neoplasms initiation was often postponed as long as possible
Detailed description
Since patients with low grade glioma are expected to become long-term survivors, the prevention of long-term sequelae is particularly important. In addition to disease progression, also treatment related side effects such as decline of neurocognitive function, endocrine impairment or sensorineural deficits can have a negative impact on patient's quality of life.
Owing to the biophysical properties of protons with an inverse depth dose profile compared to photons and a steep dose fall of to the normal tissue, there is a strong rationale for the use of PRT in the treatment of patients with low-grade glioma. Although data from large randomized trials are still missing there is increasing evidence from smaller prospective trials and retrospective analyses that the expected advantages indeed transform into clinical advantages.
However, in about 20 % of all patients, late contrast-enhancing brain lesions (CEBL) appear on follow-up MR images 6 - 24 months after treatment. At HIT in Heidelberg and at OncoRay in Dresden, CEBLs have been observed to occur at very distinct locations in the brain and relative to the treatment field. Retrospective analysis has elucidated potential key factors that lead to CEBL occurrence. However, avoidance of CEBLs is hardly feasible using conventional treatment planning strategies. Model-aided risk avoidance denotes the use of model-based CEBL risk calculations as an auxiliary tool for clinical treatment planning: Model-based risk calculations and risk reduction via software-based optimization help the clinician to minimize risk of CEBL occurrence during treatment planning.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized, observer blind two arm (active control), parallel group
| Arm | Type | Receives |
|---|---|---|
| Standard treatment plan | Active comparator | Other: standard treatment plan, no optimizationModel-based NTCP is calculated after plan approval, however, no further adjustments are to be made to the approved treatment plan |
| Optimized treatment plan | Experimental | Other: model-guided optimization of treatment planAllocated to Control Calculation of normal tissue complication probability (NTCP) Model-guided replanning. Replanning is performed with Raysearch Raystation. Optimizations objectives are: 1. the optimization objectives that control the maximum dose in the target volume employ a variable, LETd-dependent model for RBE that allows us to include the RBE-variations predicted by the NTCP model 2. the periventricular volume, defined as the volume closer than 4 mm to the ventricular wall, is included into the optimization with a constraint on its Equivalent Uniform Dose (EUD) and with the variable RBE model described above. Thereby, the combined effect of the RBE variation and increased sensitivity of the periventricular volume, as predicted by the NTCP model, is included. The effectiveness of the re-planning is verified by a second NTCP computation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- histologically proven low-grade glioma
- indication for definitive or adjuvant radiotherapy
- ability to understand character and personal consequences of the clinical trial
- written informed consent
Key exclusion criteria (4 listed)
- previous cerebral irradiation
- contraindication for contrast-enhanced MRI
- neurofibromatosis
- participation in another clinical trial with competing objectives
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| model-guided optimization of treatment planoriginal treatmant plans are optimized based on model-based NTCP | Other | Optimized treatment plan |
| standard treatment plan, no optimizationoriginal treatment plans are not optimized | Other | Standard treatment plan |
Primary outcome
incidence of contrast enhancing brain leasions
Time frame: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain
the cumulative incidence of contrast enhancing brain lesions
6 secondary outcomes
radiation-induced brain injuries
Time frame: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain
progression-free survival
Time frame: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain
overall survival
Time frame: observed within 24 months after Proton Beam Therapy (PRT) measured by quarterly contrast enhanced MRI of the brain
patient reported outcome
Time frame: up to 24 months after completion of radiotherapy
quality of life QLQ-C30
Time frame: up to 24 months after completion of PRT
quality of life QLQ-BN20
Time frame: up to 24 months after completion of PRT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Derived from this study: PubMed 39393467Sallem H, Harrabi S, Traneus E, Herfarth K, Debus J, Bauer J. A model-based risk-minimizing proton treatment planning concept for brain injury prevention in low-grade glioma patients. Radiother Oncol. 2024 Dec;201:110579. doi: 10.1016/j.radonc.2024.110579. Epub 2024 Oct 10.
- Individual participant dataSharing planned: No
Related trials for Low Grade Glioma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 2
Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
BRAF V600 Mutation, Low-grade Glioma
Active, not recruitingPhase 2
Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype
Glioma, Glioblastoma
Active, not recruitingPhase 3
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
Low-grade Glioma, Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma
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.
Adriane Lentz-Hommertgen, Phd contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing model-guided optimization of treatment plan and standard treatment plan, no optimization in people with Low Grade Glioma, run by University Hospital Heidelberg at 1 site in Germany.
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 4 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: looking for participants now, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Semi Harrabi, MD (+496221 56 ext. 8201, semi.harrabi@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of contrast enhancing brain leasions (time frame: observed within 24 months after PRT measured by quarterly contrast enhanced MRI of the brain). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05964569, which also lists 1 linked publication.
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 5 Jan 2024.