Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma

Study Overview
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Brief Summary
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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.

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

Conditions
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Glioma, Malignant

Intervention / Treatment
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* Drug: fb-PMT


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: 3+3 Dose Escalation with option for cohort expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (fb-PMT)<br>Daily subcutaneous injection of fb-PMT in four escalating cohorts to determine maximum tolerated dose, followed by treatment of up to 10 additional patients at maximum tolerated dose. | Drug: fb-PMT<br>* Daily dosing based on patient weight<br>* Other names: NP751;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of Recommended Phase 2 Dose | Maximum Tolerated Dose, as determined by Dose-Limiting Toxicities. | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, Glioblastoma Multiforme