TEMOZOLOMIDE for Glioma (WHO grade 2 or 3)

Inclusion criteria

• {"criterion_text":"- Histologically confirmed, newly diagnosed WHO grade 2 or 3 glioma."}
• {"criterion_text":"- Craniotomy or intracranial biopsy site must be adequately healed."}
• {"criterion_text":"- ≥ 2 weeks and ≤ 3 months from surgery without any interim radio- or chemotherapy or experimental intervention."}
• {"criterion_text":"- Willing and able to comply with regular neurocognitive and health-related quality of life tests/questionnaires."}
• {"criterion_text":"- Indication for postsurgical cytostatic/-toxic therapy."}
• {"criterion_text":"- Written Informed consent."}
• {"criterion_text":"- 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.1 Acceptable methods of contraception comprise barrier contraception combined with a medically accepted contraceptive method for the female patient or female partner (e.g. intra-uterine device with spermicide, hormonal contraceptive since at least 2 month). Female patients must agree not to donate lactation during treatment and until 6 months after end of study treatment."}
• {"criterion_text":"- Male patients are willing to use contraception.2 Patients should be advised to seek consultation on sperm conservation prior to treatment start. Condoms (with spermicidal jellies or cream) upon study entry and during the course treatment and 6 months after the end of treatment, have undergone vasectomy, or are practicing total abstinence. Their female partners of childbearing potential should also be advised to use contraception during this period. Sperm donation is not permitted for the same time interval."}
• {"criterion_text":"- Tumor carries an isocitrate dehydrogenase (IDH) mutation (determined by immunohistochemistry (IHC) and/or deoxyribonucleic acid (DNA) sequencing)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Biopsy (with sufficient tissue for molecular pathology) or resection."}
• {"criterion_text":"- Age: ≥18 years."}
• {"criterion_text":"- Karnofsky Performance status (KPI) ≥60%."}
• {"criterion_text":"- Life expectancy > 6 months."}
• {"criterion_text":"- Availability of formalin-fixed paraffin-embedded (FFPE) or fresh-frozen tissue and ethylenediamine tetraacetic acid (EDTA) blood for biomarker research."}
• {"criterion_text":"- Standard magnetic resonance imaging (MRI) ≤ 72 h post-surgery according to the present national and international guidelines."}

Exclusion criteria

• {"criterion_text":"- Participation in other ongoing interventional clinical trials."}
• {"criterion_text":"- Existing neuromuscular diseases, especially neural muscular atrophy with segmental demyelination (demyelinising form of Charcot-Marie-Tooth syndrome)"}
• {"criterion_text":"- Chronic constipation and subileus."}
• {"criterion_text":"- Inability to undergo MRI."}
• {"criterion_text":"- Combination treatment with mitomycin (risk of a pronounced bronchospasm and acute shortness of breath)."}
• {"criterion_text":"- Hypersensitivity to dacarbazine (DTIC)."}
• {"criterion_text":"- Patients with hereditary galactose intolerance, complete lactase deficiency or glucose-galactose malabsorption (Temodal contains Lactose)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Immunosuppression, not related to prior treatment for malignancy."}
• {"criterion_text":"- Pregnancy or breastfeeding."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients with clinical wheat allergy."}
• {"criterion_text":"- 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.)"}
• {"criterion_text":"- QTc time prolongation > 500 ms."}
• {"criterion_text":"- Patients under restricted medication for procarbazine, lomustine, vincristine and temozolomide (see list of restricted medication in Appendix 1)"}
• {"criterion_text":"- Liver disease characterized by: a. ALT or AST (≥ Grade 2 CTCAE v5.0) confirmed on two consecutive measurements OR b. 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 c. Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis"}
• {"criterion_text":"- Known uncorrected coagulopathy, platelet disorder, or history of non-drug induced thrombocytopenia."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Vaccination with life vaccines during treatment and 4 weeks before start of treatment."}

Primary endpoints

• {"endpoint_text":"- 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 the time from randomization to","definition_or_measurement_approach":"Qualified overall survival (qOS) measured as overall survival without functional/cognitive/HRQoL deterioration over 90 days; specific deterioration criteria are defined in subsequent primary endpoint items (neurocognitive decline, KPI decrease, HrQoL worsening, NANO scale decline, or death)."}
• {"endpoint_text":"- a 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* or","definition_or_measurement_approach":"NeuroCog FX® battery: decline defined as ≥1.5 SD below normative mean in ≥2 subtests and/or 90% confidence intervals indicating clinically and statistically meaningful individual change in ≥2 NeuroCog FX® raw scores."}
• {"endpoint_text":"- related to baseline: 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 (van den Bent et al. 2011), or","definition_or_measurement_approach":"Karnofsky Performance Index (KPI) decline criteria as specified (drops to defined thresholds) constitute neurological deterioration if not attributable to comorbidity or medication changes."}
• {"endpoint_text":"- related to baseline: 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) (Taphoorn et al. 2015) or","definition_or_measurement_approach":"HRQoL measured by EORTC QLQ-C30 and QLQ-BN20; worsening defined as ≥10 point deterioration in at least one of five selected domains (GHS, PF, SF, CD, MD)."}
• {"endpoint_text":"- 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 (Nayak et al. 2017).","definition_or_measurement_approach":"NANO scale: decline defined as ≥2 level worsening in ≥1 domain or worsening to highest score in ≥1 domain attributable to tumor progression (per NANO criteria)."}
• {"endpoint_text":"- death due to any cause, whatever occurs first.","definition_or_measurement_approach":"All-cause mortality; time to death recorded."}

Secondary endpoints

• {"endpoint_text":"- short-term qOS defined as qOS as described above, but neglecting the subsequent time interval of 3 months (90 days). Patients still alive without one of the above defined functional and/or cognitive deterioration criteria at a study visit or lost to follow-up will be censored at the last date they were known to be alive without deterioration.","definition_or_measurement_approach":"Short-term qOS measured similarly to qOS but ignoring events occurring after the 90-day interval; censoring rules described."}
• {"endpoint_text":"- Overall survival (OS) defined as the time from randomization until death due to any cause. Patients still alive will be censored at the last date they were known to be alive.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; standard censoring at last known alive date."}
• {"endpoint_text":"- Progression-free survival(PFS) defined as the time from randomization to the day of first documentation of clinical or radiographic tumor progression or death of any cause(whichever occurs first). Patients without a PFS event will be censored at the last disease assessment showing no progression or at baseline if patient has no post-baseline disease assessments. PFS analysis will be based on the central disease assessment by the Central Neuroradiology in the Head Clinic Heidelberg.","definition_or_measurement_approach":"PFS defined as time from randomization to first clinical or radiographic progression or death; central review by Central Neuroradiology (Head Clinic Heidelberg); censoring rules specified."}

Germany

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

495

Number Of Sites

18

Number Of Participants

406

Primary sponsor

Full Name

Universitaetsklinikum Heidelberg AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"sponsorDuties codes: 10,6,7; contact: desk email sternmann@imbi.uni-heidelberg.de","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"sponsorDuties codes: 1,12,5,7,8; contact: Submission.KKS@med.uni-heidelberg.de","organisation_type":"Hospital/Clinic/Other health care facility"}