Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma
Primary Purpose
Glioma, Malignant
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fb-PMT
Sponsored by
About this trial
This is an interventional treatment trial for Glioma, Malignant focused on measuring Glioblastoma, Glioblastoma Multiforme
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 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)
Sites / Locations
- Smilow Cancer HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (fb-PMT)
Arm 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.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Determined by the number of Treatment-Emergent Adverse Events, including Dose-Limiting Toxicities per patient.
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.
Secondary Outcome Measures
Establishment of Recommended Phase 2 Dose
Maximum Tolerated Dose, as determined by Dose-Limiting Toxicities.
Full Information
NCT ID
NCT05226494
First Posted
December 3, 2021
Last Updated
September 15, 2023
Sponsor
NanoPharmaceuticals LLC
1. Study Identification
Unique Protocol Identification Number
NCT05226494
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 23, 2022 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NanoPharmaceuticals LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioma, Malignant
Keywords
Glioblastoma, Glioblastoma Multiforme
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 Dose Escalation with option for cohort expansion
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (fb-PMT)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
fb-PMT
Other Intervention Name(s)
NP-100, NP751
Intervention Description
Daily dosing based on patient weight
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Determined by the number of Treatment-Emergent Adverse Events, including Dose-Limiting Toxicities per patient.
Time Frame
15 months
Title
Incidence of Dose Limiting Toxicities [Safety and Tolerability]
Description
Number of participants with a dose-limiting toxicity during the first cycle (28 days) of treatment at their highest dose level administered.
Time Frame
28 Days
Secondary Outcome Measure Information:
Title
Establishment of Recommended Phase 2 Dose
Description
Maximum Tolerated Dose, as determined by Dose-Limiting Toxicities.
Time Frame
28 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Adam Blanchard
Phone
(203) 499-9297
Email
adam.blanchard@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Omuro, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Smilow Cancer Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anthony Omuro, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Tolerability of Fb-PMT in Recurrent Glioblastoma
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