Clinical trial NCT05226494: Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma
Official title: A Phase 1 Trial to Evaluate the Safety and Tolerability of Fb-PMT in Patients With Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Glioma, Malignant
Keywords: Glioblastoma
Glioblastoma Multiforme
Lead sponsor: NanoPharmaceuticals LLC
Sponsor class: INDUSTRY
First posted: 2022-02-07
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: 3+3 Dose Escalation with option for cohort expansion
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 15 months
measure: Incidence of Dose Limiting Toxicities [Safety and Tolerability]
timeFrame: 28 Days
Secondary outcomes:
measure: Establishment of Recommended Phase 2 Dose
timeFrame: 28 Days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Nicholas Blondin, MD
role: PRINCIPAL_INVESTIGATOR
References: