Combining pazopanib and temozolomide for newly diagnosed glioblastoma

Inclusion Criteria:

* Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
* Age ≥ 18 years and \< 70 years
* Histologically confirmed diagnosis of GBM
* Surgically treated other than exclusive biopsy (complete or partial resection) of the GBM, for which adjuvant radiotherapy and chemotherapy is indicated
* Eligibility criteria that will need to be checked before patient registration and - No TMZ interruption resulting in hematological toxicity should has occurred
* AND the delivery of radiation dose as defined in the Stupp protocol should be at least equal to 80%
* Eastern Cooperative Oncology Group (ECOG) performance status of Glioblastoma ≤ 2
* Life expectancy\>3 months
* Measurable disease criteria : Based on the RANO criteria (Wen 2010) objective tumor response will be assessed by MRI and 18F-DOPA PET)
* Archived tumor tissue must be available for all subjects for biomarker analysis before and/or during treatment with investigational product.
* Stable doses of corticosteroid for more than 1 week.
* Adequate biological function
* Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception, as defined in Pregnancy Section in overall Safety Section during the study and for 6 months following the last dose of investigational product.

Exclusion Criteria:

* Prior malignancy.
* Surgical treatment consisting in exclusive biopsy or absence of initial surgery
* Pre-treated GBM
* Allergy to any of the tested drugs
* Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including,
* Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
* Corrected QT interval (QTc) \> 480 msecs
* History of any one or more of ardiovascular conditions within the past 6 months
* Poorly controlled hypertension
* History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
* Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
* Evidence of active bleeding or bleeding diathesis.
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
* Recent hemoptysis
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Unable or unwilling to discontinue use of prohibited medications listed in Appendix C for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study (Appendix C).
* Treatment with any of the following anti-cancer therapies:

  * radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazoapnib OR
  * chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Pazopanib
* Administration of any non-oncologic investigational drug within 30 days or 5 half-lives whichever is longer prior to receiving the first dose of study treatment
* Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity, except alopecia.