safety and tolerability of fb-pmt in recurrent glioblastoma

Conditions: Glioma, Malignant

Summary: glioblastoma is a highly aggressive and fatal form of primary malignant brain tumor with limited treatment options. fb-pmt affects a large group of cancer cell signaling pathways and thus may be effective in heterogeneous, treatment-resistant tumors such as glioblastoma. fb-pmt also is actively transported across the blood-brain barrier into the brain. this study is being conducted to determine the dose level for further clinical development of fb-pmt to treat recurrent glioblastoma.


Eligibility criteria:
inclusion criteria: * histologically proven intracranial glioblastoma, with first or second recurrence * on stable or decreasing dose of steroids, if taken prior to screening * baseline mri (with and without contrast) completed with 5 days of starting fb-pmt * prior completion of and recovery from the effects of standard of care for glioblastoma management with surgery/biopsy and radiotherapy * confirmation of true progressive disease for patients previously treated with interstitial brachytherapy or stereotactic radio surgery * life expectancy of more than three months * karnofsky performance status of ≥ 70 * hypertension must be well controlled (≤ 95th percentile) on stable doses of medication * adequate bone marrow and organ function, confirmed by laboratory testing at screening * patient or caregiver must be able to store drug under refrigerated conditions, prepare and administer daily subcutaneous injections on a set schedule, and record information in a daily treatment diary * women of childbearing potential must agree to ongoing pregnancy testing and to use medically acceptable contraception for the duration of the study and for 2 months after their last dose of study drug * males must agree to use medically acceptable contraception and refrain from donating sperm for the duration of the study and for 2 months after their last dose of study drug exclusion criteria: * significant medical illness that is uncontrolled, may obscure toxicity, may dangerously alter drug metabolism, or may compromise ability for study participation * history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off all therapy for that disease for at least 3 months prior to first dose of study drug * use of bevacizumab or any other experimental drug or therapy within 28 days of study treatment * prior therapy with fb-pmt or related drugs * currently pregnant or breastfeeding * active infection or serious intercurrent medical illness * surgery of any type within the preceding 28 days that has not fully healed * a serious or non-healing wound, ulcer, or bone fracture * a known bleeding diathesis or coagulopathy, or a history of bleeding diathesis within 28 days of study treatment * a known thrombophilic condition (i.e., protein s, protein c, or antithrombin iii deficiency, factor v leiden, factor ii g20210a mutation, homocysteinemia or antiphospholipid antibody syndrome). testing is not required in patients without thrombophilic history. * evidence of new central nervous system hemorrhage on baseline mri obtained within 14 days prior to study enrollment * clinically significant cardiovascular event such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening. * new york heart association classification of heart disease greater than class 2 * qtc interval \> 450 msec in males or \> 470 msec in females at screening * use of concomitant medications that prolong the qt/qtc interval or risk inducing torsades de pointes * use of any concomitant oatp1b1, oatp1b3, or bsep inhibitors within 14 days or five half-lives (whichever is longer) before starting study drug treatment * abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment * a significant vascular disease (e.g., aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study enrollment * history of stroke, myocardial infarction, transient ischemic attack (tia), severe or unstable angina, peripheral vascular disease, or grade ii or greater congestive heart failure within the past 6 months * history of torsades de pointes or risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long qt syndrome)

Keywords: glioblastoma glioblastoma multiforme