Glioma, Malignant
Conditions
Keywords
Glioblastoma, Glioblastoma Multiforme
Brief 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.
Interventions
DRUGfb-PMT
Daily dosing based on patient weight
Sponsors
NanoPharmaceuticals LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3+3 Dose Escalation with option for cohort expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 15 months | Determined by the number of Treatment-Emergent Adverse Events, including Dose-Limiting Toxicities per patient. |
| Incidence of Dose Limiting Toxicities [Safety and Tolerability] | 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
| Measure | Time frame | Description |
|---|---|---|
| Establishment of Recommended Phase 2 Dose | 28 Days | Maximum Tolerated Dose, as determined by Dose-Limiting Toxicities. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNicholas Blondin, MD
Yale University
Outcome results
None listed