Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma

Inclusion Criteria

• Histologically confirmed glioblastoma, recurrent after standard external-beam fractionated radiotherapy and temozolomide chemotherapy
• Patients who have NOT received any anti-angiogenic therapy (Anti-VEGF, including avastin, cediranib, or other anti-angiogenic therapies like cilengitide) on Anti-angiogenic Therapy Naive Patients Arm. No more than two recurrences are allowed on Anti-angiogenic Therapy Naive Patients Arm.
• Patients who have received any anti-angiogenic therapy (Anti-VEGF, including avastin, cediranib, or other anti-angiogenic therapies like cilengitide) on Anti-angiogenic Therapy Patients Arm. Any number of recurrences are allowed on Anti-angiogenic Therapy Patients Arm.
• Karnofsky performance status ≥ 60%
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Platelets ≥ 100 x 10^9/L
• Hemoglobin (Hgb) > 9 g/dL
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Minimum interval since completion of radiation treatment is 12 weeks
• Minimum interval since last drug therapy 2 weeks since last non-cytotoxic therapy 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
• Patients must be able to provide written informed consent
• Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant; female patients of child-bearing potential must have a negative pregnancy test
• Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission; patients with other prior malignancies must be disease-free for ≥ three years
• Patients must be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment and/or for at least 5 days before starting treatment

Exclusion Criteria

• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Patients with a history of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) within the past 6 months
• Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmias
• Clinically significant resting bradycardia
• Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (2-D) echocardiogram (ECHO) 1 cm diameter of blood seen on the MRI or CT scan. If > 1 cm of acute blood is detected, the patient will be ineligible for this trial.