Aperçu

Éligibilité

Détails de la conception

Bras et interventions

Mesures des résultats

Sites d'essai

Source : NCT05331521

Recrutement en cours

ImproveCodel: A Clinical Study to Improve Brain Function and Quality of Life of Patients With Newly Diagnosed Brain Tumors (Gliomas).

Interventionnel

Phase 3

University Hospital Mannheim, Neurology Clinic

Sponsor: University Hospital Heidelberg

Dernière synchronisation : 3 février 2026

Avis - Les informations proviennent de registres publics et peuvent ne pas refléter les changements en temps réel sur le site local.

Oligodendrogliomas in the novel edition of the Central Nervous System (CNS) World Health Organization (WHO) classification are now molecularly defined by isocitrate dehydrogenase (IDH)1 or IDH2 mutations and 1p/19q co-deletion. The prognosis of these molecularly defined tumors is to be determined in new series since survival data from older histology-based studies and population-based registries are confounded by the inclusion of 20-70% not molecularly matching subsets. Also, the optimal treatment is a matter of ongoing investigations. An extensive, but safe surgery is associated with improved outcome as is the addition of chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) to the partial brain radiotherapy (RT). However, the exact timing of postsurgical therapy especially for tumors of the WHO grade 2 and acknowledging some variability in grading as well as the choice of chemotherapy, temozolomide instead of PCV (CODEL: NCT00887146 randomizing CNS WHO grade 2 and 3 oligodendrogliomas to chemoradiation(CHRT)therapy with PCV or with temozolomide) or the need for primary radiotherapy RT are subjects of clinical studies (POLCA: NCT02444000 randomizing patients with newly diagnosed CNS WHO grade 3 oligodendrogliomas to standard CHRT with PCV or PCV alone). Given the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumor located in the brain optimizing care is the major challenge.

NOA-18/IMPROVE CODEL aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG), thereby delaying radiotherapy (RT) and adding the chemoradiotherapy (CHRT) concept at progression after initial radiation-free chemotherapy, allowing for an effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life (QOL) deterioration regardless whether tumor progression or toxicity is the main cause.

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Catégorie de traitement

Autres médicaments, Autres non-médicaments

Mutations requises

IDH

Essai commencé

7 avril 2021

Dernière mise à jour par le sponsor

3 février 2026

Achèvement estimé

31 mars 2033

Contact de l'étude

Nom:Wolfgang Wick, Prof. Dr.

E-mail:wolfgang.wick@med.uni-heidelberg.de

Téléphone:+49 6221 56

Nom:Antje Wick, PD Dr.

E-mail:antje.wick@med.uni-heidelberg.de

Téléphone:+49 6221 56

Éligibilité

Critères d'inclusion

1. Histologically confirmed, newly diagnosed CNS WHO grade 2 or 3 glioma.

2. Tumor carries an isocitrate dehydrogenase (IDH) mutation (determined by immunohistochemistry (IHC) and/or deoxyribonucleic acid (DNA) sequencing).

3. Tumor is co-deleted for 1p/19q (determined by copy number variations, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) or other appropriate methods).

4. Biopsy (with sufficient tissue for molecular pathology) or resection.

5. Age: ≥18 years.

6. Karnofsky Performance status (KPI) ≥60%.

7. Life expectancy >6 months.

8. Availability of formalin-fixed paraffin-embedded (FFPE) or fresh-frozen tissue and ethylenediamine tetraacetic acid (EDTA) blood for biomarker research.

9. Standard magnetic resonance imaging (MRI) ≤ 72 h post-surgery according to the present national and international guidelines.

10. Craniotomy or intracranial biopsy site must be adequately healed.

11. ≥ 2 weeks and ≤ 3 months from surgery without any interim radio- or chemotherapy or experimental intervention.

12. Willing and able to comply with regular neurocognitive and health-related quality of life tests/questionnaires.

13. Indication for postsurgical cytostatic/-toxic therapy.

14. Written Informed consent.

15. Female patients with reproductive potential have a negative pregnancy test (serum or urine) day -6 until day 0 of screening (and 3 days prior to first IMP-intake or RT). Female patients are surgically sterile or agree to use adequate contraception during the period of therapy and 7 months after the end of study treatment, or women have been postmenopausal for at least 2 years.

16. Male patients are willing to use contraception

Critères d'exclusion

1. Participation in other ongoing interventional clinical trials.

2. Inability to undergo MRI.

3. Abnormal (≥ Grade 2 CTCAE v5.0 laboratory values for hematology (Hb, WBC, neutrophils, or platelets), liver (serum bilirubin, ALT, or AST) or renal function (serum creatinine).

4. Clinically active tuberculosis; known HIV infection or active Hepatitis B (HBV) or Hepatitis C (HCV) infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients' blood or tissue (e.g. rabies).

5. Any prior anti-cancer therapy or co-administration of anti-cancer therapies other than those administered/allowed in this study. History of low-grade glioma that did not require prior treatment with chemotherapy or radiotherapy is not an exclusion criterion.

6. Immunosuppression, not related to prior treatment for malignancy.

7. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 5 years unless the patient has been disease-free for 5 years.

8. Any clinically significant concomitant disease (including hereditary fructose intolerance) or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.

9. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.

10. Pregnancy or breastfeeding.

11. History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product. (E.g.: In the discretion of the investigator patients are allowed to take part in the study even if they suffer from celiac disease: Cecenu contains very small amounts of gluten (from wheat starch). It is considered gluten-free and is tolerated by patients suffering from celiac disease. One capsule contains no more than 4 micrograms of Gluten.)

12. QTc time prolongation >500 ms.

13. Patients under restricted medication for procarbazine, lomustine, vincristine and temozolomide.

14. Liver disease characterized by:

1. ALT or AST (≥ Grade 2 CTCAE v5.0) confirmed on two consecutive measurements OR

2. Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices (≥ Grade 2 CTCAE v5.0) OR

3. Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis.

15. Known uncorrected coagulopathy, platelet disorder, or history of non-drug induced thrombocytopenia.

16. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis; autoimmune-related hypothyroidism (patients on a stable dose of thyroid replacement hormone are eligible for this study) and type I diabetes mellitus (patients on a stable dose of insulin regimen are eligible for this study).

17. Vaccination with life vaccines during treatment and 4 weeks before start of treatment.

18. Existing neuromuscular diseases, especially neural muscular atrophy with segmental demyelination (demyelinising form of Charcot-Marie-Tooth syndrome).

19. Chronic constipation and subileus.

20. Combination treatment with mitomycin (risk of a pronounced bronchospasm and acute shortness of breath).

21. Hypersensitivity to dacarbazine (DTIC).

22. Patients with hereditary galactose intolerance, complete lactase deficiency or glucose-galactose malabsorption (Temodal contains Lactose).

23. Patients with clinical wheat allergy.

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Détails de la conception

AllocationRandomized

Modèle d'interventionParallel Assignment

MasquageNone (Open Label)

Nombre à inscrire406

Bras et interventions

Bras

Interventions

Type : Active Comparator

Description : Radiotherapy (RT) for over approximately 5-6 weeks: * at 50.4/54 Gy in 1.8 Gy fractions for grade 2 and * at 59.4 Gy in 1.8 Gy fractions for grade 3 gliomas PCV cycles are 6 weeks long and given as: * Day 1: Lomustine (CCNU) at 110 mg/m2 body surface orally, * Days 8/29: Vincristine 1.4 mg/m2 i.v. (capped at 2 mg), * Days 8-21: Procarbazine 60 mg/m2 orally (capped at 100 mg).

Interventions :

CETEG
PCV
RT

Mesures des résultats

Mesures des résultats primaires

Qualified overall survival (qOS)Counted as event starting 12 months (365 days) after randomization on 2 consecutive study visits with an interval of 3 months (90 days) till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

The primary efficacy endpoint is the overall survival without functional and/or cognitive and/or quality of life deterioration over a period of 90 days, coined qualified overall survival (qOS).

Short-term qOS deterioration in NeuroCogFX®Counted as event starting 12 months (365 days) after randomization on 2 consecutive study visits with an interval of 3 months (90 days) till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

The primary efficacy endpoint is overall survival without functional and/or cognitive and/or quality of life deterioration over a period of 90 days, coined qualified overall survival (qOS). Short-term qOS is defined as detriment of ≥ 1.5 standard deviations below the normative mean (i.e. percentile rank ≤ 6.68) in two or more NeuroCog FX® subtests AND Related to baseline: 90%-confidence intervals of NeuroCog FX® subtests indicate a clinically and statistically meaningful individual change (i.e. deterioration) in two or more NeuroCog FX® subtest raw scores

Short-term qOS deterioration in KPICounted as event starting 12 months (365 days) after randomization on 2 consecutive study visits with an interval of 3 months (90 days) till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

The primary efficacy endpoint is overall survival without functional and/or cognitive and/or quality of life deterioration over a period of 90 days, coined qualified overall survival (qOS). Short-term qOS is defined as a decrease in the KPI from 100 or 90 to 70 or less, a decrease in KPI of at least 20 from 80 or less, or a decrease in KPI from any baseline to 50 or less. Fulfilment of one of these criteria is considered neurological deterioration unless attributable to comorbid events or changes in corticosteroid dose.

Short-term qOS deterioration in HrQoLCounted as event starting 12 months (365 days) after randomization on 2 consecutive study visits with an interval of 3 months (90 days) till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

The primary efficacy endpoint is overall survival without functional and/or cognitive and/or quality of life deterioration over a period of 90 days, coined qualified overall survival (qOS). Short-term qOS is defined as a worsening of at least 10 points, which is the minimal clinically relevant difference, in at least one of the five selected domains of the HrQoL (global health status (GHS), physical functioning (PF), social functioning (SF), determined in the QLQ-C30 with higher scores indicate better HRQoL; communication deficits (CD) & motor dysfunction (MD) determined by QLQ-BN20 with lower scores indicate better HRQoL).

Short-term qOS deterioration in NANO scaleCounted as event starting 12 months (365 days) after randomization on 2 consecutive study visits with an interval of 3 months (90 days) till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

The primary efficacy endpoint is overall survival without functional and/or cognitive and/or quality of life deterioration over a period of 90 days, coined qualified overall survival (qOS). Short-term qOS is defined as a decline in the NANO scale defined as a ≥2 level worsening from baseline within ≥1 domain or worsening to the highest score within ≥1 domain that is felt to be related to underlying tumor progression and not attributable to a comorbid event or change in concurrent medication.

Short-term qOS deterioration due to deathFrom start of randomization until death from any cause till the end of follow up at 120 months.

Death due to any cause.

Mesures des résultats secondaires

Short-term qOSFrom 3 months after start of treatment, every 3 months till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

Defined qOS defined as qOS as described above, but neglecting the subsequent time interval of 3 months (90 days).

Overall survival (OS)From start of randomization until death from any cause till the end of follow up at 120 months.

Defined as the time from randomization until death due to any cause.

Progression-free survival (PFS)From randomization until the day of first documentation of clinical or radiographic tumor progression or death of any cause till the end of follow up at 120 months or date of death from any cause, whatever occurs first.

Defined as the time from randomization to the day of first documentation of clinical or radiographic tumor progression or death of any cause.

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Sites d'essai

Cette étude compte 18 sites d'essai

University Hospital Mannheim, Neurology Clinic

Mannheim, DE

Recrutement en cours

Mannheim, 68167 DE

University Hospital Mannheim, Neurology Clinic

Recrutement en cours

Berlin, 10117 DE

Charité, University Medicine Berlin, Neurosurgery

Recrutement en cours

Bochum, 44892 DE

Knappschaftskrankenhaus Bochum GmbH, Neurology Clinic

Recrutement en cours

Bonn, 53127 DE

University Hospital Bonn, Neurology Clinic

Recrutement en cours

Chemnitz, 09116 DE

Chemnitz Hospital, Neurosurgery

Recrutement en cours

Cologne, 50937 DE

University Hospital Cologne, Neurosurgery

Recrutement en cours

Frankfurt, 60528 DE

University Hospital Frankfurt, Neurooncology

Recrutement en cours

Göttingen, 37075 DE

University Hospital Göttingen, Neurosurgery

Recrutement en cours

Homburg, 66421 DE

University Hospital Saarland, Neurosurgery

Recrutement en cours

Jena, 07747 DE

University Hospital of Jena, Neurosurgery

Recrutement en cours

Leipzig, 04103 DE

University Hospital Leipzig, Radiation Therapy

Recrutement en cours

Minden, 32429 DE

University Clinic Muehlenkreis, Minden

Recrutement en cours

Munich, 81675 DE

University Hospital rechts der Isar, Radiation Oncology

Recrutement en cours

Regensburg, 93053 DE

University Hospital Regensburg, Neurology Clinic

Recrutement en cours

Schwerin, 19049 DE

Helios Hospital Schwerin, Neurosurgery

Recrutement en cours

Würzburg, 97080 DE

University Hospital Wuerzburg, Neurosurgery

Recrutement en cours

Düsseldorf, 40225 DE

University Hospital Duesseldorf, Neurooncology

Recrutement en cours

Tübingen, 72076 DE

University Hospital Tuebingen, Neurooncology

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