Glioblastoma
Conditions
Interventions
Trade Name: VOTRIENT
Product Name: VOTRIENT
Product Code: GW786034
Pharmaceutical Form: Tablet
Sponsors
CENTRE ANTOINE LACASSAGNE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Deviations from inclusion criteria are not allowed because deviations can potentially jeopardize the scientific integrity of the study, regulatory acceptability, or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. 1) 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. Note: Informed consent may be obtained prior to start of the specified screening window. Note: Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study such as bone scan) and obtained prior to signing of informed consent, may be utilized for screening or baseline purpose,s provided these procedures are conducted as specified in the protocol 2) Age = 18 years and 3 months 8) Measurable disease criteria : Based on the RANO criteria (Wen 2010) objective tumor response will be assessed by MRI and 18F-DOPA PET) 9) Archived tumor tissue must be available for all subjects for biomarker analysis before and/or during treatment with investigational product. 10) Stable doses of corticosteroid for more than 1 week. 12) 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. 13) Patient with a social security category (French regulatory). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: Deviations from exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. 1. prior malignancy. 2. Surgical treatment consisting in exclusive biopsy or absence of initial surgery 3. Pre-treated GBM 4. Allergy to any of the tested drugs 5. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: • Active peptic ulcer disease • Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn’s disease), or other gastrointestinal conditions with increased risk of perforation • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. 6. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: • Malabsorption • Major resection of the stomach or small bowel. 7. Corrected QT interval (QTc) > 480 msecs Note: Correction method should be reported in CRT 8. History of any one or more of the following cardiovascular conditions within the past 6 months: • Cardiac angioplasty or stenting • Myocardial infarction • Unstable angina • Coronary artery bypass graft surgery • Symptomatic peripheral vascular disease • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (To be added as an Appendix in the protocol) 9. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study. 10. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible 11. 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). 12. Evidence of active bleeding or bleeding diathesis. 13. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). • Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I -To evaluate the Recommended Phase 2 Dose (RP2D) of pazopanib in oral route in addition to the maintenance phase of the Stupp protocol. -To evaluate the Maximal Tolerated Dose (MTD i.e the highest dose administered for which > 33% of patients experienced a DLT i.e an adverse event which severity may limit the escalation of the doses) associated with the concomitant administration of pazopanib during the maintenance phase of the “Stupp protocol”. Phase II -To evaluate the efficacy (Progression-Free-Survival rate at 6 Months ie. Rate of no progression at 6 months) of pazopanib in oral route in addition to the maintenance phase of the Stupp protocol. ;Secondary Objective: -To define the overall tolerance of pazopanib associated with TMZ during the maintenance phase of the “Stupp protocol”. -To assess the antitumor activity of the adjunction of daily dose of pazopanib to the maintenance phase of the Stupp protocol according to the Revised Assessment in Neuro-Oncology (RANO) criteria (response rate) and the median duration of response. -To determine the median Progression-Free-Survival (mPFS), the PFS rate at 12 (PFS-12) months. -To determine the median Overall Survival (mOS), the OS rate at 6 (OS-6) and 12 (OS-12) months. -To determine the pharmacokinetics (PK) profile of pazopanib when given in combination with TMZ. -To determine the pharmacokinetics (PK) profile of TMZ when given in combination with pazopanib. Ancillary study: -Pharmacogenetics and pharmacogenomics analysis of VEGF family. -To characterize tumor response to treatment by the association of MRI and 18F-DOPA PET imaging. ;Primary end point(s): Phase I -To evaluate the Recommended Phase 2 Dose (RP2D) of pazopanib in oral route in addition to the maintenance phase of the Stupp protocol. -To evaluate the Maximal Tolerated Dose (MTD i.e the highest dose administered for which > 33% of patients experienced a DLT i.e an adverse event which severity may limit the escalation of the dos | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -To define the overall tolerance of pazopanib associated with TMZ during the maintenance phase of the “Stupp protocol”. -To assess the antitumor activity of the adjunction of daily dose of pazopanib to the maintenance phase of the Stupp protocol according to the Revised Assessment in Neuro-Oncology (RANO) criteria (response rate) and the median duration of response. -To determine the median Progression-Free-Survival (mPFS), the PFS rate at 12 (PFS-12) months. -To determine the median Overall Survival (mOS), the OS rate at 6 (OS-6) and 12 (OS-12) months. -To determine the pharmacokinetics (PK) profile of pazopanib when given in combination with TMZ. -To determine the pharmacokinetics (PK) profile of TMZ when given in combination with pazopanib. Ancillary study: -Pharmacogenetics and pharmacogenomics analysis of VEGF family. -To characterize tumor response to treatment by the association of MRI and 18F-DOPA PET imaging. ;Timepoint(s) of evaluation of this end point: 6 and 12 month of treatment | — |
Countries
France
Contacts
Public ContactDr ESMA SAADA
CENTRE ANTOINE LACASSAGNE
Outcome results
None listed