Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamic Effects of PQR309 in Glioblastoma Patients

Exclusion Criteria

• •1. Second or later glioblastoma relapse
• •2. Received more than one systemic treatment regimen for glioblastoma
• •3. Patients receiving enzyme-inducing anti-epileptic drug (EIAED) within 7 days of the first dose of PQR309
• •4. Patient is taking a drug with known risk to promote QT prolongation and Torsades de Pointes.
• •5. Patient is currently using herbal preparations or medications. Patient should stop using herbal medications 7 days prior to the first dose of the study drug
• •6. Patients with glioblastoma known to contain IDH1 or 2 mutation
• •7. Other concomitant anti-tumor therapy as determined by the study team
• •8. Prior treatment with intracerebral agents, e.g. prolifeprospan 20 with carmustine wafer
• •9. Patients unable to undergo contrast-enhanced MRI
• •10. Fasting glucose \> 7.0 mmol/L or HbA1c \> 6.4%.
• •11. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders.
• •12. Anxiety ≥CTC AE grade 3
• •13. Patient has an uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, known HIV infection, chronic liver disease, chronic renal disease, pancreatitis, chronic pulmonary disease, active cardiac disease or cardiac dysfunction, interstitial lung disease, active autoimmune disease, uncontrolled diabetes, neuropsychiatric or social situations that would limit compliance with the study requirements
• •14. Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
• •15. Concomitant treatment with medicinal products that increase the pH (reduce acidity) of the upper gastrointestinal tract, including, but not limited to, proton-pump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients may be enrolled in the study after a wash-out period sufficient to terminate their effect (See section 11.2.2.8).Women who are pregnant or breast feeding,
• •16. Women able to conceive and unwilling to practice an effective method of birth control\* from screening until 90 days after discontinuing study treatment (women of childbearing potential\*\* must have a negative urine or serum pregnancy test within 7 days prior to first dose of PQR309
• •* Adequate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), or double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Male patients must agree to use condoms as contraception method.
• •* Child-bearing potential for the sake of this study is defined as sexually mature women who have not undergone a hysterectomy, have not been naturally postmenopausal for at least 12 consecutive months or have a serum FSH \< 40 mIU/ml.