TN-TC11G (THC+CBD) Combination With Temozolomide and Radiotherapy in Patients With Newly-diagnosed Glioblastoma

Inclusion Criteria:

• Ability to understand and sign the informed consent document

• Men or women ≥18 years and ≤70 years

• Newly-diagnosed GB confirmed by biopsy or by resection in the 4-7 weeks before beingregistered in the trial.

• Patients must have at least 15 slides without staining or a tissue block (frozen orparaffin-embedded) available from a previous biopsy or surgery (tumour samplepreviously archived).

• Patients must have recovered from previous surgeries (time between surgery andinclusion in the study: 6 weeks).

• Karnofsky Index ≥60%.

• Adequate bone marrow reserve: haemoglobin ≥10 g/dL, WBC >3,000/mcL, absoluteneutrophil count (ANC) ≥1,500 cells/μL, platelets ≥100,000 cells/μL.

• Adequate liver function: Bilirubin <1.5 times the upper limit of normal (ULN); AST ≤2.5 x ULN

• Creatinine clearance >60 ml/min/1.73 m2.

• The study treatment's effects on the development of the human foetus are not known.For this reason, women of childbearing age and men must agree to use a suitablebirth control method (hormonal, barrier, abstinence or surgical sterilisation)before inclusion in the study, for the duration of the study and for at least 3months after completing the trial treatment. The definition of an effective methodof birth control is based on the judgement of the principal investigator or theirdesignee. If a woman is pregnant or there is suspicion that she might be pregnantwhile participating in the study, she must inform the trial doctor immediately. Allwomen of childbearing age should have a negative pregnancy test (serum/urine) in the 2 weeks prior to the beginning of treatment.

Exclusion Criteria:

• Presence of extracranial metastatic disease.

• Any previous treatment for glioblastoma.

• Patients who have had a Gliadel implant in the surgery.

• Use of an enzyme-inducing antiepileptic drug. Patients receiving this type of drugmust have a washout period of at least 7 days prior to study inclusion.

• Previous abuse of cannabinoids.

• Presence of any clinically significant gastrointestinal abnormality that may affectthe intake, transit or absorption of the study drug, such as the inability to takemedication in the form of oral tablets or solution.

• Presence of any psychiatric or cognitive impairment that limits understanding or thesigning of the informed consent and/or compromises compliance with the requirementsof this protocol.

• Significant or uncontrolled cardiovascular disease, including: 1. Myocardialinfarction in the previous 12 months. 2. Uncontrolled angina in the previous 6months. 3. Congestive heart failure in the previous 6 months. 4. Diagnosed orsuspected congenital long QT syndrome. 5. History of ventricular arrhythmias of anyclinically significant type (such as ventricular tachycardia, ventricularfibrillation or torsades de pointes). 6. QTc prolongation on an electrocardiogramprior to entry (>470 ms). 7. History of second- or third-degree heart block (thesepatients may be eligible if they carry pacemakers). 8. Heart rate <50/min on thebaseline electrocardiogram. 9. Uncontrolled hypertension

• Any patient with a history of significant cardiovascular disease, even if it iscurrently controlled, or who presents signs or symptoms that suggest impaired leftventricular function according to the investigator should have an assessment of leftventricular ejection fraction (LVEF) by ECCO or MUGA. If the LVEF in thesecircumstances is below the site's lower limit of normality or less than 50%, thepatient will not be eligible.

• History of any cancer, except in the following circumstances: Patients with ahistory of other malignancies are eligible if they have been disease-free for atleast the last 3 years and if, in the investigator's opinion, there is a low risk ofdisease recurrence. People with the following cancers are eligible, even if theyhave been diagnosed and treated in the past 3 years: cervical carcinoma in situ andbasal cell carcinoma.

Patients will not be eligible if there is evidence of another cancer that required therapy other than surgery in the past 3 years.