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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

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 2 or 3 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
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CETEG
Treatment: Drugs - PCV
Treatment: Other - RT

Active comparator: RT PCV - 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).

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: 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.

Treatment: Drugs: PCV
In the comparator arm there is the option for second radiotherapy or even reuse of the full radiochemotherapy regimen as it had been given at diagnosis (BIC).

Treatment: Other: RT
Radiotherapy at 50.4/54 Gy in 1.8 Gy fractions for grade 2 and 59.4 Gy in 1.8 Gy fractions for grade 3 gliomas
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Qualified overall survival (qOS)
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
Short-term qOS deterioration in NeuroCogFX®
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Short-term qOS deterioration in KPI
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Short-term qOS deterioration in HrQoL
Timepoint [4] 0 0
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.
Primary outcome [5] 0 0
Short-term qOS deterioration in NANO scale
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Short-term qOS deterioration due to death
Timepoint [6] 0 0
From start of randomization until death from any cause till the end of follow up at 120 months.
Secondary outcome [1] 0 0
Short-term qOS
Timepoint [1] 0 0
From 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.
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
From start of randomization until death from any cause till the end of follow up at 120 months.
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
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.

Eligibility
Key inclusion criteria
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) 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.
16. 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
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).

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
31/03/2031
Actual
Sample size
Target
406
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Baden-Württemberg
Country [2] 0 0
Germany
State/province [2] 0 0
Berlin
Country [3] 0 0
Germany
State/province [3] 0 0
Bochum
Country [4] 0 0
Germany
State/province [4] 0 0
Bonn
Country [5] 0 0
Germany
State/province [5] 0 0
Chemnitz
Country [6] 0 0
Germany
State/province [6] 0 0
Cologne
Country [7] 0 0
Germany
State/province [7] 0 0
Duesseldorf
Country [8] 0 0
Germany
State/province [8] 0 0
Frankfurt
Country [9] 0 0
Germany
State/province [9] 0 0
Göttingen
Country [10] 0 0
Germany
State/province [10] 0 0
Homburg
Country [11] 0 0
Germany
State/province [11] 0 0
Jena
Country [12] 0 0
Germany
State/province [12] 0 0
Leipzig
Country [13] 0 0
Germany
State/province [13] 0 0
Mannheim
Country [14] 0 0
Germany
State/province [14] 0 0
Minden
Country [15] 0 0
Germany
State/province [15] 0 0
Munich
Country [16] 0 0
Germany
State/province [16] 0 0
Regensburg
Country [17] 0 0
Germany
State/province [17] 0 0
Schwerin
Country [18] 0 0
Germany
State/province [18] 0 0
Tuebingen
Country [19] 0 0
Germany
State/province [19] 0 0
Würzburg

Funding & Sponsors
Primary sponsor type
Other
Name
University Hospital Heidelberg
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Universitätsmedizin Mannheim
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Ruhr University of Bochum
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05331521