Tamoxifen Versus Etoposide After First Recurrence in GBM Patients

Inclusion Criteria:

1. Histologically proven GBM with progression after previous first linechemoradiotherapy with temozolomide.

2. Progression documented by MRI with at least one bi-dimensionally measurable targetlesion with one diameter of at least 10 mm, visible on two or more axial slices 5 mmapart.

3. Not received radiotherapy within the three months before the diagnosis ofprogression.

4. Stable or decreasing dose of corticosteroids prior to randomization: corticosteroids (dexamethasone) should be given at the lowest dose needed to control symptomsarising from increased intracerebral edema.

5. ECOG performance 0-2 (Appendix 2).

6. Age from 18-65 years.

7. Women of child bearing potential (WOCBP) must have a negative serum (or urine)pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP isdefined as any female who has experienced menarche and who has not undergonesurgical sterilization (hysterectomy or bilateral oophorectomy or bilateralsalpingectomy) and is not postmenopausal. Menopause is defined as 12 months ofamenorrhea in a woman over age 45 years in the absence of other biological orphysiological causes.

8. Patients of childbearing / reproductive potential should use adequate birth controlmethods, as defined by the investigator, during the study treatment period and for aperiod of 60 days after the last dose of study drug. A highly effective method ofbirth control is defined as those that result in low failure rate (i.e. less than 1%per year) when used consistently and correctly. Note: abstinence is acceptable if this is established and preferred contraceptionfor the patient and is accepted as a local standard.

9. Laboratory evaluation obtained within 7 days prior to randomization, with adequatefunction as defined below:

• ANC ≥ 1.5 x 109/L

• Platelets ≥ 100 x 109/L

• Serum creatinine ≤ 1.5 times ULN

• Total serum bilirubin ≤ 1.5 times ULN

• ALT < 3 times ULN

• AST < 3 times ULN

• Alkaline phosphatase < 3 times ULN

10. Patient must understand and sign an informed consent prior to study registration.

Exclusion Criteria:

1. History of another malignancy or a concurrent malignancy (exceptions includepatients who have been disease-free for 3 years, or patients with a history ofcompletely resected non-melanoma skin cancer or successfully treated in situcarcinoma are eligible, for example cervical cancer in situ.

2. Uncontrolled hypertension (systolic blood pressure >150 mm Hg or diastolic bloodpressure >100 mm Hg).

3. Any arterial or venous thrombosis up to 6 months before registration.

4. Evidence of recent hemorrhage on brain MRI.

5. Substantial cardiovascular disease: cerebral vascular accident/stroke (<6 monthsprior to enrollment), myocardial infarction (<6 months prior to enrollment),unstable angina, congestive heart failure (> New York Heart AssociationClassification Class II), or serious cardiac arrhythmia requiring medication.