This phase II trial studies how well dovitinib works in treating patients with recurrent or progressive glioblastoma. Dovitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
PRIMARY OBJECTIVES: Anti-angiogenic Therapy Naive Patients: To determine 6 month progression-free survival (PFS6) in anti-angiogenic therapy (including anti-vascular endothelial growth factor (VEGF) therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM) in patients treated with dovitinib Anti-angiogenic Therapy Patients: To estimate time to progression in patients with recurrent or progressive Glioblastoma who have progressed on anti-angiogenic therapy (including anti-VEGF therapy). SECONDARY OBJECTIVES: 1. To evaluate the side effect profile of dovitinib in both patient populations. 2. To evaluate the efficacy of dovitinib as measured by objective response rate (ORR) in both patient populations. 3. To estimate time to percentage of patients free from progression at 6 months (PFS-6)in patients with recurrent or progressive Glioblastoma who have progressed on antiangiogenic therapy (including anti-VEGF therapy). (Anti-angiogenic Therapy Patients) 4. To estimate time to progression in anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naiVe patients with recurrent glioblastoma (GBM) in patients treated with dovitinib. (Anti-angiogenic Therapy Naive Patients) 5. To evaluate the overall survival (OS) in both patient populations. EXPLORATORY OBJECTIVES: To explore association between clinical outcome and potential biomarkers that may include microparticles, PlGF, PDGF-AA, PDGF-AB, PDGF-BB, SDF-1a, thrombospondin-1, Ang1, and Il-6, IL-8 and FGF. OUTLINE: Patients receive dovitinib orally (PO) 5 days a week. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Given PO
Correlative studies
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Arm 1: Progression Free Survival (PFS)
Number of anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM). The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6. Progression is defined using the Response Assessment in Neuro-Oncology (RANO) Criteria where CR = Total disappearance of lesions, PR = \>50% reduction in lesions and SD = \<25% reduction in lesions
Time frame: 6 months
Arm 2: Determine Median Time to Progression
Anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) patients with recurrent glioblastoma (GBM). Time to tumor progression (TTP), is defined as the time from randomization to time of progressive disease. So it is ongoing and will be assessed every 8 weeks …8, 16, 24, 32 …week. Progression is defined as \>25% increase in size of lesions or evidence of new lesions
Time frame: From randomization to time of progression every 8 weeks (2 cycles of treatment) up to 32 weeks
Toxicity Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Number of adverse events in patients in both populations (grade 1-5). Grade 1 are defined as mild events characterized as asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention indicated. Grade 2 are moderate events with minimal, local or non invasive interventions indicated. Grade 3 are severe or medically significant events but not immediately life-threatening; hospitalization indicated. Grade 4 are life-threatening consequences with urgent intervention indicated. Grade 5 are deaths related to events
Time frame: Assessed until 30 days after treatment up to 32 weeks
Objective Response Rate Using Modified Revised Assessment in Neuro-Oncology (RANO) Criteria
Number of patients (both populations) with a complete response (CR-no measurable disease), partial response (PR \>50% reduction in measurable disease), minor response (MR \>25% reduction of measurable disease), stable disease (SD \<25% reduction) and progressive disease (PD \>25% measurable disease and new lesions).
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Time frame: Up to 30 days after treatment
Median Progression Free Survival
The progression- free survival (PFS) at 6 months is defined as the time from randomization to objective tumor progression or death. So patients who have CR, PR or SD at 6 months will constitute PFS-6
Time frame: 6 months
Overall Survival
The Kaplan-Meier method will be used. Overall survival is defined as the time from randomization to death.
Time frame: to death, approximately 2 years