Dovitinib in Treating Patients With Recurrent or Progressive Glioblastoma
Condition: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Tumor
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: dovitinib; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        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) < 50% or lower limit of normal (whichever is higher)
                       or multi gated acquisition scan (MUGA) < 45% or lower limit of normal
                       (whichever is higher)

                    -  Any of the following within 6 months prior to starting study drug:
                       myocardial infarction (MI), severe/unstable angina, coronary artery bypass
                       graft (CABG), congestive heart failure (CHF), cerebrovascular accident
                       (CVA), and transient ischemic attack (TIA)

                    -  Uncontrolled hypertension defined by a systolic blood pressure (SBP) ≥ 160
                       mm Hg and/or diastolic blood pressure (DBP) ≥ 100 mm Hg, with or without
                       anti-hypertensive medication(s)

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea,
             vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

          -  Cirrhosis, chronic active hepatitis or chronic persistent hepatitis

          -  Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
             mandatory)

          -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
             active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
             safety risks or compromise compliance with the protocol

          -  Women of child-bearing potential, who are biologically able to conceive, not employing
             two forms of highly effective contraception; highly effective contraception (e.g. male
             condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used
             by both sexes during the study and must be continued for 8 weeks after the end of
             study treatment; oral, implantable, or injectable contraceptives may be affected by
             cytochrome P450 interactions, and are therefore not considered effective for this
             study; women of child-bearing potential, defined as sexually mature women who have not
             undergone a hysterectomy or who have not been naturally postmenopausal for at least 12
             consecutive months (e.g., who has had menses any time in the preceding 12 consecutive
             months), must have a negative serum pregnancy test ≤ 14 days prior to starting study
             treatment

          -  Fertile males not willing to use contraception, as stated above

          -  Patients who are currently receiving full dose anticoagulation treatment with
             therapeutic doses of warfarin or anti-platelet therapy (e.g., Plavix [clopidogrel
             bisulfate]); treatment with locally accepted low molecular weight heparin and low dose
             of acetylsalicylic acid (i.e., 81mg or 100 mg daily) to prevent cardiovascular events
             or strokes is allowed

          -  Patients unwilling or unable to comply with the protocol

          -  Any significant hemorrhage defined as > 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.