None listed
Conditions
Interventions
Trade Name: Sutent
Product Name: Sunitinib
Product Code: L01XE04
Pharmaceutical Form: Capsule
Trade Name: Belustine
Product Name: Lomustine
Product Code: L01AD02
Pharmaceutical Form: Capsule
Sponsors
VU University Medical Center, Department of Medical Oncology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Signed (by the patient or legally acceptable representative) and dated Informed Consent Form 2. Histologically confirmed de novo or secondary glioblastoma with unequivocal first progression, at least 3 months off radiotherapy. 3. No more than one line of chemotherapy (concurrent and adjuvant temozolomide based chemotherapy including in combination with another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization. 4. Patients may have undergone surgery for recurrence. If operated, residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence. 5. No radiotherapy, stereotactic radiosurgery or brachytherapy as treatment for recurrence. 6. Patients must have a Karnofsky Performance Score = 70% 7. Patients need to have adequate hematological, renal and hepatic function as assessed by the following laboratory requirements to be conducted within seven days prior to start study treatment: 7a. Hemoglobin = 7.0 mmol/L 7b. Absolute neutrophil count (ANC) = 1.5 x 109/L 7c. Platelet count = 100 x 109/L 7d. ALAT and ASAT = 2.5 x ULN 7e. Serum creatinine eGFR = 50 ml/min 7f. Albumin = 25 g/L 8. Age = 18 years 9. Male and female patients with reproductive potential must use an approved contraceptive method during and for three months after discontinuation of study treatment. 10. Patients must be able to swallow oral medication. 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 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Evidence of a significant uncontrolled concomitant disease, such as cardiovascular disease (including stroke, New York Heart Association Class III or IV cardiac disease or myocardial infarction within 6 months prior to screening, unstable arrhythmia, clinically significant valvular heart disease and unstable angina); nervous system, pulmonary (including obstructive pulmonary disease and history of symptomatic bronchospasm), renal, hepatic, endocrine, or gastrointestinal disorders; or a serious non-healing wound or fracture. 2. Patients with a prior (< 5 years) or concomitant second malignancy. 3. Prior radiotherapy in the abdomen or in the lungs or in more than 3 vertebrae in the spine (Less than 3 vertebrae are considered a small radiation field and eligibility will be decided on an individual basis from the PI) 4. Poorly controlled hypertension despite adequate blood pressure medication. Blood pressure must be = 160/95 mmHg at the time of screening on a stable antihypertensive regimen. Blood pressure must be stable on at least 2 separate measurements. 5. Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infection of the nail beds.) 6. Initial MR-scan of the brain showing intratumoral hemorrhage, except for stable post-operative grade 1 hemorrhage. 7. Known hypersensitivity to sunitinib or to its excipients. 8. Presence of any significant central nervous system or psychiatric disorder(s) that would interfere with the patient’s compliance. 9. Use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes. 10. Use of strong hepatic enzyme-inducing antiepileptic drugs, such as carbamazepine, phenobarbital and phenytoin. If a patient uses one or more of these specific antiepileptic drugs, the must switch to an antiepileptic drug that does not interact with cytochrome P450 (CYP450) liver enzymes, such as levetiracetam, prior to the start of study treatment. 11. Drug or alcohol abuse. 12. Females who are pregnant or breast-feeding. 13. Any evidence of a disease or condition that might affect compliance with the protocol or interpretation of the study results or render the patient at high risk from treatment complications. 14. Unwillingness or inability to comply with study and follow-up procedures. 15. Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. To determine the effect of high-dose sunitinib on overall survival (OS 9, OS 12) in patients with recurrent GBM. 2. To assess the objective radiological response rate, using the RANO criteria. 3. To assess the safety and toxicity during treatment. 4. To assess patient-oriented criteria: steroid use and health-related quality of life (reported by patients and caregivers/relatives). 5. To explore the potential value of blood markers for molecular diagnostics, disease and response monitoring. 6. To explore if MGMT promoter methylation status modulates the response to sunitinib. ;Primary end point(s): - Six-month progression-free survival (PFS6);Timepoint(s) of evaluation of this end point: Disease will be assessed by study-specific MRI according to an uniform protocol every 6 weeks for the first 6 months and every 12 weeks thereafter;Main Objective: To determine the effect of high-dose sunitinib versus standard treatment with lomustine on six-month progression-free survival (PFS6) in patients with recurrent GBM. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival 2. Objective radiological response rate 3. Toxicity and side effects. 4a. Steroid use 4b. Health-related Quality of Life (HRQoL) 5. Blood markers (i.e. tumor-educated platelets) 6. MGMT promoter methylation status;Timepoint(s) of evaluation of this end point: 1. Until death, survival follow-up will take place every 12 weeks. 2. Every 6 weeks for the first 6 months and every 12 weeks thereafter by study-specific MRI. 3. Every hospital visit using the CTCAE version 4.0. 4a. Steroid use will be documented every hospital visit. 4b. QoL-assessment takes place every 6 weeks via the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires 5. Additional blood samples will be drawn on five specific time points: 1) at baseline, 2) at the first outpatient visit, 3) after two weeks of treatment, 4) at the first response evaluation (first MRI) and 5) at the time of progression. 6. At the end of the study, the MGMT methylation status will be correlated with the response to treatment | — |
Countries
Netherlands
Contacts
Public ContactDepartment of Medical Oncology
VU University Medical Center
Outcome results
None listed