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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05331521




Registration number
NCT05331521
Ethics application status
Date submitted
15/03/2022
Date registered
15/04/2022
Date last updated
8/05/2024

Titles & IDs
Public title
A Clinical Study to Improve Brain Function and Quality of Life of Patients With Newly Diagnosed Brain Tumors (Gliomas).
Scientific title
Improvement of Functional Outcome for Patients With Newly Diagnosed Grade II or III Glioma With Co-deletion of 1p/19q - IMPROVE CODEL: the NOA-18 Trial
Secondary ID [1] 0 0
2018-005027-16
Secondary ID [2] 0 0
NOA-18
Universal Trial Number (UTN)
Trial acronym
ImproveCodel
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oligodendroglioma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cream vehicle
Treatment: Drugs - CETEG

Active comparator: RT PCV - Radiotherapy (RT) for over approximately 5-6 weeks:

* at 50.4/54 Gy in 1.8 Gy fractions for grade II and
* at 59.4 Gy in 1.8 Gy fractions for grade III 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).

Experimental: CETEG - Six 42-day cycles of lomustine plus temozolomide according to the commonly used regimen:

* Day 1: Lomustine (CCNU) at 100 mg/m2
* Days 2-6: Temozolomide at 100 mg/m2 (cycles 1) and in 50 mg/m2 steps to 200 mg/m2 from cycle 2 on dependent on hematological toxicity


Treatment: Drugs: Cream vehicle
The cream vehicle is similar to the delgocitinib cream except that it does not contain any active medical ingredient.

Treatment: Drugs: CETEG
At progression, patients without prior radiotherapy will undergo radiotherapy and PCV as an adjunct chemotherapy if bone marrow reserve allows in the experimental arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
* Histologically confirmed, newly diagnosed WHO grade II or III glioma.
* Tumor carries an isocitrate dehydrogenase (IDH) mutation (determined by immunohistochemistry (IHC) and/or deoxyribonucleic acid (DNA) sequencing).
* 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).
* Open biopsy or resection.
* Age =18 years.
* Karnofsky Performance Index (KPI) =60%.
* Life expectancy > 6 months.
* Availability of formalin-fixed paraffin-embedded (FFPE) or fresh-frozen tissue and ethylenediamine tetraacetic acid (EDTA) blood for biomarker research.
* Standard magnetic resonance imaging (MRI) = 72 post-surgery according to the present national and international guidelines.
* Craniotomy or intracranial biopsy site must be adequately healed.
* = 2 weeks and = 3 months from surgery without any interim radio- or chemotherapy or experimental intervention.
* Willing and able to comply with regular neurocognitive and health-related quality of life tests/questionnaires.
* Indication for postsurgical cytostatic/-toxic therapy.
* Written Informed consent.
* Female patients with reproductive potential have a negative pregnancy test (serum or urine) within 6 days prior to start of therapy. Female patients are surgically sterile or agree to use adequate contraception during the period of therapy and 6 months after the end of study treatment, or women have been postmenopausal for at least 2 years.
* Male patients are willing to use contraception.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participation in other ongoing interventional clinical trials.
* Insufficient tumor material for molecular diagnostics.
* Inability to undergo MRI.
* Abnormal (= Grade 2 CTCAE v5.0) laboratory values for hematology (Hb, WBC (White Blood Cell), neutrophils, or platelets), liver (serum bilirubin, ALT (Alanine Amino Transferase), or AST (Aspartate Amino Transferase)) or renal function (serum creatinine).
* 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).
* 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.
* Immunosuppression not related to prior treatment for malignancy.
* 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.
* 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.
* 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.
* Pregnancy or breastfeeding.
* 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.
* QTc (corrected QT interval) time prolongation > 500 ms.
* Patients under restricted medication for procarbazine, lomustine, vincristine and temozolomide.
* Liver disease characterized by:

* ALT or AST (= Grade 2 CTCAE v5.0) confirmed on two consecutive measurements OR
* 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
* Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
* Known uncorrected coagulopathy, platelet disorder, or history of non-drug induced thrombocytopenia.
* 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, Sjogren's syndrome, Guillain-Barre 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).
* Vaccination with life vaccines during treatment and 4 weeks before start of treatment.
* Existing neuromuscular diseases, especially neural muscular atrophy with segmental demyelination (demyelinising form of Charcot-Marie-Tooth syndrome)
* Chronic constipation and subileus
* Combination treatment with mitomycin (risk of a pronounced bronchospasm and acute shortness of breath)
* Hypersensitivity to dacarbazine (DTIC)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2029
Actual
Sample size
Target
406
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Other
Name
University Hospital Heidelberg
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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 II 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.
Trial website
https://clinicaltrials.gov/study/NCT05331521
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Wolfgang Wick, Prof. Dr.
Address 0 0
University Hospital Heidelberg
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Wolfgang Wick, Prof. Dr.
Address 0 0
Country 0 0
Phone 0 0
+49 6221 56
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05331521