Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma

Sponsor
NanoPharmaceuticals LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05226494
Collaborator
(none)
28
1
1
25.3
1.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
28 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
3+3 Dose Escalation with option for cohort expansion3+3 Dose Escalation with option for cohort expansion
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Trial to Evaluate the Safety and Tolerability of Fb-PMT in Patients With Recurrent Glioblastoma
Actual Study Start Date :
Jun 23, 2022
Anticipated Primary Completion Date :
Aug 1, 2023
Anticipated Study Completion Date :
Aug 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (fb-PMT)

Daily subcutaneous injection of fb-PMT in three 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
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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 Outcome Measures

    1. Establishment of Recommended Phase 2 Dose [28 Days]

      Lesser of Optimum Biological Dose (determined by pharmacokinetic analysis) or Maximum Tolerated Dose (determined by Dose-Limiting Toxicities)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Smilow Cancer Hospital New Haven Connecticut United States 06511

    Sponsors and Collaborators

    • NanoPharmaceuticals LLC

    Investigators

    • Principal Investigator: Anthony Omuro, MD, Yale University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    NanoPharmaceuticals LLC
    ClinicalTrials.gov Identifier:
    NCT05226494
    Other Study ID Numbers:
    • NP-100-101
    First Posted:
    Feb 7, 2022
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by NanoPharmaceuticals LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 19, 2022