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

Inclusion Criteria:

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

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

3. Tumor is co-deleted for 1p/19q (determined by copy number variations, fluorescencein 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 andethylenediamine tetraacetic acid (EDTA) blood for biomarker research.

9. Standard magnetic resonance imaging (MRI) ≤ 72 h post-surgery according to thepresent 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 orexperimental intervention.

12. Willing and able to comply with regular neurocognitive and health-related quality oflife 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 orurine) 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 duringthe period of therapy and 7 months after the end of study treatment, or women havebeen postmenopausal for at least 2 years.

16. Male patients are willing to use contraception

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) orHepatitis C (HCV) infection, or active infections requiring oral or intravenousantibiotics or that can cause a severe disease and pose a severe danger to labpersonnel working on patients' blood or tissue (e.g. rabies).

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

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

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

8. Any clinically significant concomitant disease (including hereditary fructoseintolerance) or condition that could interfere with, or for which the treatmentmight interfere with, the conduct of the study or the absorption of oral medicationsor that would, in the opinion of the Principal Investigator, pose an unacceptablerisk to the patient in this study.

9. Any psychological, familial, sociological, or geographical condition potentiallyhampering compliance with the study protocol requirements and/or follow-upprocedures; those conditions should be discussed with the patient before trialentry.

10. Pregnancy or breastfeeding.

11. History of hypersensitivity to the investigational medicinal product or to any drugwith similar chemical structure or to any excipient present in the pharmaceuticalform of the investigational medicinal product. (E.g.: In the discretion of theinvestigator patients are allowed to take part in the study even if they suffer fromceliac disease: Cecenu contains very small amounts of gluten (from wheat starch). Itis considered gluten-free and is tolerated by patients suffering from celiacdisease. 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 andtemozolomide.

14. Liver disease characterized by:

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

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

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

18. Written Informed consent.
 

19. 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.
 

20. Male patients are willing to use contraception
 
 Exclusion Criteria:
 

21. Participation in other ongoing interventional clinical trials.
 

22. Inability to undergo MRI.
 

23. 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).
 

24. 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).
 

25. 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.
 

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

27. 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.
 

28. 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.
 

29. 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.
 

30. Pregnancy or breastfeeding.
 

31. 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.)
 

32. QTc time prolongation >500 ms.
 

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

34. Liver disease characterized by:
 

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

36. 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
 

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

38. Known uncorrected coagulopathy, platelet disorder, or history of non-drug inducedthrombocytopenia.

39. 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 antiphospholipidsyndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,multiple sclerosis, vasculitis, or glomerulonephritis; autoimmune-relatedhypothyroidism (patients on a stable dose of thyroid replacement hormone areeligible for this study) and type I diabetes mellitus (patients on a stable dose ofinsulin regimen are eligible for this study).

40. Vaccination with life vaccines during treatment and 4 weeks before start oftreatment.

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

42. Chronic constipation and subileus.

43. Combination treatment with mitomycin (risk of a pronounced bronchospasm and acuteshortness of breath).

44. Hypersensitivity to dacarbazine (DTIC).

45. Patients with hereditary galactose intolerance, complete lactase deficiency orglucose-galactose malabsorption (Temodal contains Lactose).

46. Patients with clinical wheat allergy.