A phase II/III study of high-dose, intermittent sunitinib in patients with recurrent GBM

1. Signed (by the patient or legally acceptable representative) and dated
Informed Consent Form
2. Histologically confirmed primary 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:
a. Hemoglobin >= 7.0 mmol/L
b. Absolute neutrophil count (ANC) >= 1.5 x 109/L
c. Platelet count >= 100 x 109/L
d. ALAT and ASAT <= 2.5 x ULN
e. Serum creatinine eGFR >= 50 ml/min
f. 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.

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.