A Phase 1 Trial to Evaluate the Safety and Tolerability of Fb-PMT in Patients With Recurrent Glioblastoma

Primary Outcome Measures  :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 15 months ]Determined by the number of Treatment-Emergent Adverse Events, including Dose-Limiting Toxicities per patient.
   
2. Incidence of Dose Limiting Toxicities [Safety and Tolerability] [ Time Frame: 28 Days ]Number of participants with a dose-limiting toxicity during the first cycle (28 days) of treatment at their highest dose level administered.
   

Secondary Outcome Measures  :

1. Establishment of Recommended Phase 2 Dose [ Time Frame: 28 Days ]Lesser of Optimum Biological Dose (determined by pharmacokinetic analysis) or Maximum Tolerated Dose (determined by Dose-Limiting Toxicities)

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 Cytochrome P450 (CYP) inhibitors or CYP inducers 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)