fb-PMT for Glioblastoma

Overseen By Amy L Rodrigues, CCRC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NanoPharmaceuticals LLC

Must not be taking: Bevacizumab, QT prolonging drugs

Disqualifiers: Uncontrolled illness, Other cancer, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called fb-PMT for glioblastoma, a challenging brain cancer. Researchers aim to determine if fb-PMT can help by affecting multiple cancer cell signals and effectively penetrating the brain. The trial will test various doses to identify the optimal amount. Individuals with recurrent glioblastoma, who have previously undergone standard treatments like surgery and radiation, and can manage daily injections, may be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use certain medications that affect heart rhythm or specific liver transport proteins within 14 days before starting the study drug. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that fb-PMT is likely to be safe for humans?

Research has shown that fb-PMT targets and disrupts cancer cell pathways and can effectively reach brain tumors like Glioblastoma by crossing the blood-brain barrier. Although specific safety data from previous studies is unavailable, this trial is in its early stages, focusing on determining safe dosage levels of fb-PMT. Treatments in this phase are often tested in humans for the first time, so detailed safety data might not yet be available. However, reaching this stage usually indicates earlier research suggesting the treatment could be safe enough for human testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which often involve surgery, radiation, and chemotherapy, fb-PMT offers a novel approach by using a daily subcutaneous injection. Researchers are particularly excited about fb-PMT because it is being tested to determine the maximum tolerated dose through escalating cohorts, potentially allowing for a more personalized and effective dosing strategy. Additionally, this method of administration could lead to fewer side effects compared to traditional treatments, making it a promising option for patients seeking less invasive alternatives.

What evidence suggests that fb-PMT might be an effective treatment for Glioblastoma?

Research has shown that fb-PMT, the treatment under study in this trial, could be a promising option for glioblastoma, an aggressive brain tumor. Studies have found that fb-PMT can significantly reduce tumor growth and kill over 90% of cancer cells in lab tests. This treatment targets multiple cancer cell processes, potentially making it effective against these difficult-to-treat tumors. Notably, fb-PMT can pass through the blood-brain barrier, a challenge for many cancer drugs. Early indications suggest it could aid in treating glioblastoma, but further research is needed to confirm its effects in people. ^{1 3 6 7 8}

Who Is on the Research Team?

Nicholas Blondin, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with recurrent glioblastoma, a type of brain tumor. Participants must have had prior treatment, be on stable steroids if used, and have good performance status. They should not be pregnant or breastfeeding, have serious heart conditions or bleeding disorders, nor can they take certain medications that affect the heart rhythm.

Inclusion Criteria

I am on a stable or decreasing dose of steroids.

My brain cancer has returned for the first or second time.

Baseline MRI (with and without contrast) completed with 5 days of starting fb-PMT

Exclusion Criteria

I haven't had a stroke, heart attack, severe heart issues, or major blood vessel problems in the last 6 months.

I haven't had major blood vessel problems like aneurysms or clots in the last 6 months.

Evidence of new central nervous system hemorrhage on baseline MRI obtained within 14 days prior to study enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

What Are the Treatments Tested in This Trial?

Interventions

• fb-PMT

Trial Overview

The study tests fb-PMT's safety and tolerability to determine the appropriate dose for treating recurrent glioblastoma. It involves daily subcutaneous injections by patients or caregivers who must also maintain a treatment diary.

How Is the Trial Designed?

Group I: Treatment (fb-PMT) Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

NanoPharmaceuticals LLC

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Glioblastoma (GBM) patients currently have a poor prognosis, with a median survival of only 14-16 months, highlighting the need for improved treatment strategies.

Recent advancements in physical treatment methods, such as fluorescent guided surgery and tumor-treating fields therapy, have shown positive results in clinical trials and are now part of standard care, while other techniques like photodynamic therapy and focused ultrasound are in development and require further validation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical approaches to treat glioblastoma. Latifyan, S., de Micheli, R., Hottinger, AF.[2021]

This study is the largest real-world analysis of health-related quality of life outcomes for patients using tumor treating fields (TTFields) therapy for glioblastoma, involving 1,106 respondents from a pool of 2,815 patients.

Results indicated that longer time using TTFields therapy was associated with improved quality of life measures, such as mobility and self-care, particularly in patients with disease progression, while older age and disease progression negatively impacted quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life for Patients Receiving Tumor Treating Fields for Glioblastoma. Palmer, JD., Chavez, G., Furnback, W., et al.[2022]

In a study of nine UK patients with glioblastoma, Tumour Treating Fields (TTF) showed high compliance at 89%, indicating that patients were able to integrate this treatment into their care effectively.

TTF was well-tolerated with minimal side effects, and patients reported no significant decline in quality of life until late in the disease, suggesting it can be a beneficial addition to standard therapy for glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour treating fields in glioblastoma: is the treatment tolerable, effective, and practical in UK patients? Olubajo, F., Thorpe, A., Davis, C., et al.[2023]

In a study of 13 glioblastoma patients, using O-(2-18 F-fluoroethyl)-L-tyrosine (FET)-PET for defining radiation target volumes resulted in significantly better coverage of recurrent tumor volumes compared to traditional MRI-based methods, with a median coverage of 100% versus 85%.

The FET-PET-based planning target volume (PTV) was also significantly smaller than the MRI-based PTV (median 160 ml vs. 231 ml), suggesting that this approach could reduce side effects while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapse patterns after radiochemotherapy of glioblastoma with FET PET-guided boost irradiation and simulation to optimize radiation target volume. Piroth, MD., Galldiks, N., Pinkawa, M., et al.[2022]

F-FET PET imaging is effective in distinguishing late pseudoprogression from true tumor recurrence in glioblastoma multiforme, with diagnostic accuracy indicated by areas under the receiver operating characteristic curve ranging from 0.80 to 0.88.

Different analytical methods for interpreting F-FET PET images showed similar effectiveness, but those focusing on areas of highest uptake performed slightly better, highlighting the need for standardization in imaging techniques across medical centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of Different Approaches for Detection of Late Pseudoprogression in Glioblastoma With O-(2-[18F]Fluoroethyl)-L-Tyrosine PET. Kertels, O., Mihovilovic, MI., Linsenmann, T., et al.[2019]

In a pilot study involving 17 patients with glioblastoma, the use of dual timepoint FET-PET imaging for planning simultaneous integrated boost (SIB) radiotherapy showed promising survival outcomes, with 1-year overall survival at 73% and progression-free survival at 53%.

While the treatment did not show excessive neurotoxicity, radiation necrosis was a common side effect, occurring in 7 patients, highlighting the need for careful monitoring in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Irradiation Boost Based on 18F-FET-PET in Patients with Newly Diagnosed Glioblastoma. Harat, M., Blok, M., Miechowicz, I., et al.[2022]

Recent treatments for glioblastoma multiforme (GBM), such as regorafenib, paxalisib, and VAL-083, show promise in slowing disease progression, with VAL-083 being notable for its ability to cross the blood-brain barrier and target DNA directly.

Clinical trials indicate that therapies like selinexor and innovative vaccines have provided initial benefits in extending survival, while maintaining a positive safety profile, though more research is needed to confirm these findings and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocytological Advances in the Treatment of Glioblastoma Multiforme. Fiani, B., Covarrubias, C., Onyedimma, C., et al.[2021]

The combination of bevacizumab (BEV) and fotemustine (FTM) showed a response rate of 46.6% and a disease control rate of 90.9% in 176 patients with recurrent glioblastoma multiforme (GBM), indicating significant clinical activity.

Patients with a higher Karnofsky Performance Status (KPS) and methylated MGMT status experienced longer progression-free survival (PFS), suggesting these factors may be important prognostic indicators for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of bevacizumab in combination with fotemustine in chinese patients with recurrent glioblastoma multiforme. Liu, Z., Zhang, G., Zhu, L., et al.[2022]

A novel cranial window technique was developed for repairing surgical defects after glioblastoma (GBM) resection, achieving a 75% gross total resection rate in a rodent model.

Surgical intervention resulted in 100% survival at 4 weeks post-surgery, compared to 0% survival in non-surgical controls, with no observed neurological defects or infections, indicating the method's safety and potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of an imageable surgical resection animal model of Glioblastoma (GBM). Sweeney, KJ., Jarzabek, MA., Dicker, P., et al.[2019]

In a study using mechanical compression to simulate compressive solid stress (CSS) in glioblastoma (GBM) cell lines, LN229 cells showed increased migration and elongation at 23 Pa, indicating a potential mechanism for tumor aggressiveness.

The differential response to CSS between GBM cell lines suggests that targeting specific miRNAs, particularly from the miR548 family, could be a promising strategy for developing therapies that improve patient outcomes in GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility. Calhoun, MA., Cui, Y., Elliott, EE., et al.[2021]

Proton-beam therapy (PBT) for recurrent glioblastoma (GBM) was found to be well tolerated, with only one patient experiencing acute grade 3 toxicity and four experiencing late grade 3 toxicity, indicating a low risk of severe side effects.

In a study of 45 patients, median progression-free survival (PFS) was 13.9 months and median overall survival (OS) was 14.2 months after PBT reirradiation, suggesting that PBT offers effective treatment outcomes comparable to traditional photon reirradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry. Saeed, AM., Khairnar, R., Sharma, AM., et al.[2022]

ImuVert, a biologic response modifier derived from Serratia marcescens, has been granted orphan drug status by the FDA and is currently being tested in a multicenter clinical trial for recurrent malignant astrocytoma, a type of brain tumor with a poor prognosis.

In phase I and II trials, ImuVert showed manageable toxicities, including mild local reactions and some cases of hypotension, indicating that while it has potential as a treatment, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ImuVert therapy in the treatment of recurrent malignant astrocytomas: nursing implications. Cress, NB., Owens, BM., Hill, FH.[2019]

Tumour treating fields (TTFs) are FDA approved for treating high-grade gliomas and are currently being tested for their effectiveness in pediatric brain tumors and intracranial metastatic disease as an additional therapy alongside standard treatments.

The review highlights the importance of assessing TTFs not only for their efficacy but also for safety, patient compliance, and cost considerations in various brain tumor pathologies beyond glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour Treating Fields (TTFs) for Paediatric Brain Tumours, Brain Metastases and other Novel Applications. Mirza, FA., Shamim, MS.[2019]

Patients with glioblastoma multiforme who underwent complete tumor resection had a significantly better survival rate compared to those who only had a biopsy, with a 3.82-fold greater chance of death for biopsy patients.

Among the chemotherapy options, temozolomide was associated with the longest survival rates, outperforming both carmustine (BCNU) and the PCV regimen (procarbazine/lomustine/vincristine).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting the survival of patients with glioblastoma multiforme. Nikolov, V., Stojanovic, M., Kostic, A., et al.[2019]

In a systematic review of 19 trials involving 755 glioblastoma multiforme patients, combining molecularly targeted therapies (MTT) with radiotherapy (RT) resulted in a higher incidence of severe adverse events (SAE) compared to standard therapy, with a pooled incidence rate of 131.2 per 1000 person-months versus 74.7 for standard therapy.

Despite the increased risk of SAEs, the combination of MTT and RT did not show significant improvements in progression-free survival (PFS) or overall survival (OS) compared to standard treatments, indicating that while MTT may lead to more side effects, it does not enhance survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of phase I/II targeted therapy combined with radiotherapy in patients with glioblastoma multiforme: quality of report, toxicity, and survival. dos Santos, MA., Pignon, JP., Blanchard, P., et al.[2018]

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