BKM120 is a potent and highly specific oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, currently under investigation in a first-in-man study in patients with advanced solid tumors (wild type and PIK3CA-mutated). Consistent, dose-dependent pharmacodynamic activity has been demonstrated and clear signs of anti-tumor activity have been seen with BKM120.
Name: BKM120Description: BKM120 will be administered on a continuous once daily dosing schedule at a dose of 100 mg (p.o.)until progression of disease or unacceptable toxicity or a maximum of 4 weeks.Type: Drug
Description: Biomarkers assessments must be performed at baseline and at the end of study treatment. The following biomarkers will be assessed: PI3K, KRAS, pAkt and -RPS6pMeasure: - To determine the grade of inhibition of PI3K/mTOR pathways, in pre-surgery setting with BKM120 Time: 28 days
Single Group Assignment
There is one SNP
- Patients must meet the following laboratory criteria within 7 days prior to start the study treatment: - Hematology - Neutrophil count of > 1200/mm3 - Platelet count of > 100,000/ mm3 - Hemoglobin > 90g/L - Biochemistry - AST/SGOT and ALT/SGPT < 2.5 x upper limit of normal (ULN) or < 5.0 x ULN if the transaminase elevation is due to liver metastases - Total bilirubin < 1.5 x ULN [Patients with Gilbert Syndrome must have total bilirubin < 3 ULN] - Cholesterol < ULN - 7.75 mmol/L and Triglycerides < ULN - 2.5 x ULN (with lipid-lowering drugs permitted) - Serum creatinine < 1.5 x ULN or 24-hour creatinine clearance > 60 mL/min - Serum albumin > LLN or > 30 g/L - Fasting plasma glucose ≤ 140 mg/dL (7.8 mmol/L) Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor - Patients with a known hypersensitivity to BKM120 or to its excipients - Patients with a history of photosensitivity reactions to other drugs - Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire: - 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 (immediate risk of doing harm to others) - ≥ CTCAE grade 3 anxiety The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment. --- P13K ---