Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma

NanoPharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Glioma, Malignant

Treatments: Drug: fb-PMT

Study type: Interventional

Funder types: Industry

Identifiers

NCT05226494

NP-100-101

Details and patient eligibility

About

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.

Enrollment: 34 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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34 participants in 1 patient group

Treatment (fb-PMT)

Experimental group

Description:

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.

Treatment:

Drug: fb-PMT