Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma

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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioma, Malignant
• Intervention / Treatment: Drug: fb-PMT

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amy L Rodrigues, CCRC; Phone Number: (203) 260-9632; Email: amy.rodrigues@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Smilow Cancer Hospital
      • Principal Investigator: Nicholas Blondin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (fb-PMT); 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; Daily dosing based on patient weight; Other Names: NP-100; NP751

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NanoPharmaceuticals LLC
• Investigators: Principal Investigator: Nicholas Blondin, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: January 25, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Glioblastoma Multiforme; Glioblastoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma
• Other Study ID Numbers: NP-100-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No