BPM31510 + Vitamin K1 for Glioblastoma

Not currently recruiting at 10 trial locations

Overseen By Seema Nagpal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BPGbio

Must not be taking: Anticoagulants, Digitalis, Antiangiogenics, Theophylline

Disqualifiers: Cerebral hemorrhage, Cardiac history, Coagulopathies, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with newly diagnosed glioblastoma, a type of brain cancer. It combines the experimental drug BPM31510 (also known as Coenzyme Q10 injectable nanosuspension) with Vitamin K1, radiation therapy, and a common chemotherapy drug called TMZ. The goal is to determine if adding BPM31510 can improve treatment outcomes. This trial may suit those who have not yet received treatments like radiation or chemotherapy for their glioblastoma and are within 50 days of surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, you cannot take therapeutic doses of anticoagulants (blood thinners), digitalis alkaloids (heart medications), antiangiogenic drugs (cancer treatments), or theophylline (a medication for breathing problems).

Is there any evidence suggesting that BPM31510 is likely to be safe for humans?

Research has shown that BPM31510 has been tested for safety in humans. It has been studied in patients with high-grade glioma, a type of brain tumor. In these studies, BPM31510 was generally well-tolerated. The most common side effects were mild, such as tiredness and nausea. Some patients experienced more serious side effects, but these were less common.

BPM31510 also contains ubidecarenone, known as CoQ10. CoQ10 is already used safely as a dietary supplement and in treatments for heart conditions, supporting its safety.

Overall, despite some side effects, BPM31510 is considered safe enough for further testing in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Most treatments for glioblastoma involve the standard combination of surgery, radiation therapy (RT), and the chemotherapy drug temozolomide (TMZ). But BPM31510 offers a different approach by potentially reprogramming the metabolism of cancer cells. This treatment is unique because it includes a new active ingredient, BPM31510, which is delivered through a 96-hour infusion, coupled with Vitamin K1. Researchers are excited about BPM31510 because it targets cancer cell metabolism in a novel way, which might enhance the efficacy of existing treatments like RT and TMZ, potentially leading to better outcomes for patients with glioblastoma.

What evidence suggests that BPM31510 might be an effective treatment for glioblastoma?

Research has shown that BPM31510, which uses a form of CoQ10, can target and kill glioblastoma cells by exploiting their unique energy processes. In earlier studies, patients treated with BPM31510 demonstrated promising results in slowing tumor growth. Specifically, data from phase 2 trials indicated that many patients had stable disease after 6 months, and some even after 12 months. In this trial, participants will receive BPM31510 combined with Vitamin K1, radiation therapy, and the chemotherapy drug TMZ. These findings suggest that BPM31510 could be effective in treating glioblastoma when used alongside standard treatments like radiation and chemotherapy. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed glioblastoma who haven't had prior treatments like radiation or chemotherapy. They should be able to understand the study and consent, have a life expectancy of at least 3 months, and a Karnofsky score of 60 or more. Participants must not be pregnant, avoid pregnancy during the trial, and be two weeks post-surgery.

Inclusion Criteria

It has been at least 14 days since my surgery.

Life expectancy ≥3 months

I have been newly diagnosed with a glioblastoma.

Exclusion Criteria

I have taken drugs like Avastin recently or plan to in the next 2 weeks.

I am currently taking heart medication such as Digoxin.

You are allergic to CoQ10.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-confirmation

Establish safety of BPM31510 in combination with RT and TMZ using a 3+3 dose design

8 weeks

Weekly visits for infusion

Treatment

Participants receive BPM31510 infusion and concurrent RT and TMZ chemotherapy

8 weeks

Weekly visits for infusion and daily RT and TMZ

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 8 weeks for the first year, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BPM31510

Trial Overview

The study tests BPM31510 combined with Vitamin K1 alongside standard treatment (radiation therapy and TMZ chemotherapy) for glioblastoma. It's an open-label Phase 2 trial where all participants receive this combination to see how effective it is compared to traditional methods alone.

How Is the Trial Designed?

Group I: BPM31510, Vitamin K1, RT and TMZ Experimental Treatment 4 Interventions

Subjects will receive a BPM31510 96hr infusion once weekly for 8 wk. Prophylactic Vitamin K1 at a recommended dose of 10 mg will be given subcutaneously to all subjects prior to the beginning of each week of therapy. After 2 wk of treatment with BPM31510, subjects will start concurrent standard RT and TMZ 75 mg/m2 once daily (qd) × 42 days. Subjects will receive the standard TMZ treatment for up to 12 cycles post BPM31510 treatment.

Who Is Running the Clinical Trial?

BPGbio

Lead Sponsor

Trials

13

Recruited

2,200+

Berg, LLC

Lead Sponsor

Trials

13

Recruited

2,200+

BPGbio

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

Lipid-soluble vitamins, particularly A, D, and E, have shown potential in modulating biomarkers related to glioblastoma (GBM) pathophysiology, with 40 differentially expressed biomarkers identified from 19 studies.

Retinoids from vitamin A promote cell differentiation and inhibit stemness in GBM cells, while vitamin D affects cell cycle biomarkers, and vitamin E derivatives influence apoptosis, suggesting these vitamins could be explored as alternative therapeutic strategies for GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma. Osman, DE., Phon, BWS., Kamarudin, MNA., et al.[2022]

Coenzyme Q10 (CoQ10) significantly reduced tumor volume in glioblastoma multiforme (GBM) models by decreasing hypoxia and vascularization, while also limiting inflammatory cell infiltration.

CoQ10's effects on GBM were linked to the downregulation of key proteins like HIF-1α and NF-kB, leading to changes in tumor cell behavior, including reduced migration and invasion, suggesting it could be a valuable addition to current GBM therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CoQ10 reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation. Frontiñán-Rubio, J., Llanos-González, E., García-Carpintero, S., et al.[2023]

Nanocapsules containing coenzyme Q10 and vitamin E acetate effectively protect coenzyme Q10 from degradation under UVC radiation, with higher concentrations of vitamin E enhancing this protective effect.

In vitro tests showed that these nanocapsules significantly reduced the viability of malignant glioma and melanoma cells by 61% and 66%, respectively, indicating their potential as effective delivery systems for these compounds in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved photostability and cytotoxic effect of coenzyme Q10 by its association with vitamin E acetate in polymeric nanocapsules. Pegoraro, NS., Mattiazzi, J., da Silveira, EF., et al.[2018]

Vitamin K3 demonstrated significant growth inhibition of glioblastoma multiforme cells, with an IC50 value of 23 microM, indicating its potential as an effective treatment option for this aggressive cancer.

In contrast, vitamin K2 showed only a modest effect, inhibiting growth in glioblastoma multiforme cells at much higher concentrations (IC50 values of 960 and 970 microM), while vitamin K1 had no impact on cell growth at all.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro. Oztopçu, P., Kabadere, S., Mercangoz, A., et al.[2013]

Ubidecarenone, a form of coenzyme Q10 used in heart failure therapy, was found to have no genotoxic effects when produced through bacteria fermentation, based on rigorous testing methods including the Ames test and chromosome aberration test.

The study confirms the safety profile of ubidecarenone manufactured by bacteria fermentation, indicating it does not cause genetic mutations or chromosomal damage, which is important for its use as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotoxicity studies of ubidecarenone (coenzyme Q10) manufactured by bacteria fermentation. Yamaguchi, N., Nakamura, K., Oguma, Y., et al.[2019]

Coenzyme Q10 (CoQ10) nanosuspensions, particularly those stabilized with PEG32 stearate, showed promising characteristics for lung delivery via nebulization, achieving a high respirable fraction of 70.6% and a small particle size of 3.02μm, which is ideal for effective inhalation.

Stability tests indicated that the formulation with vitamin-E TPGS was the most stable over 90 days, and in vitro studies demonstrated that the formulations containing lecithin and PEG32 stearate were non-toxic to human lung cells, suggesting a safe profile for potential therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy. Rossi, I., Sonvico, F., McConville, JT., et al.[2018]

Ubidecarenone, delivered through BPM31510, shows a significant therapeutic potential against glioblastoma, as it selectively targets cancer cells with elevated oxidative stress, leading to increased sensitivity compared to non-cancer cells.

In vivo studies demonstrated that treatment with ubidecarenone resulted in over 25% long-term survival in a rodent glioma model, indicating its effectiveness in enhancing survival in aggressive cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High levels of ubidecarenone (oxidized CoQ10) delivered using a drug-lipid conjugate nanodispersion (BPM31510) differentially affect redox status and growth in malignant glioma versus non-tumor cells. Sun, J., Patel, CB., Jang, T., et al.[2021]

Ubidecarenone (CoQ(10)) has been shown to be safe in toxicological studies, with no evidence of mutagenic potential at high doses, including up to 2000 mg/kg/day in mice.

The studies demonstrated that ubidecarenone did not cause chromosomal aberrations or reverse mutations in various tests, indicating its safety for human consumption, especially given its long history of use in foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the mutagenic potential of ubidecarenone using three short-term assays. Kitano, M., Hosoe, K., Fukutomi, N., et al.[2014]

In a study involving 483 pregnancies and 615 blood samples, low maternal Coenzyme Q10 (CoQ10) levels were associated with spontaneous abortions and threatened late abortions, suggesting that CoQ10 could serve as a marker for pathological uterine activity.

Fetal CoQ10 levels were significantly elevated in cases of non-immune fetal hydrops, indicating that increased CoQ10 may be linked to fetal distress or hypoxia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The antioxidants (coenzyme Q10) in materno-fetal physiopathology]. Noia, G., Romano, D., De Santis, M., et al.[2014]

The study demonstrated that transdermal delivery systems (TDS) for Coenzyme Q10 (CoQ10) can be effectively developed, with formulations containing 6% linoleic or oleic acid showing the highest permeation rates.

In vivo pharmacokinetic results indicated that TDS with oleic acid provided a favorable absorption profile, with lower peak concentration and prolonged effects compared to oral administration, suggesting a potentially safer and more effective delivery method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation and evaluation of ubidecarenone transdermal delivery systems. Jung, SY., Kang, EY., Choi, YJ., et al.[2014]

Coenzyme Q10 enhances the growth and viability of glioma cells in serum-free conditions by restoring mitochondrial function and increasing energized mitochondria.

The mechanism behind this effect involves a decrease in intracellular reduced glutathione, which activates key signaling pathways including proteinkinase C, ERK1/2, and phosphoinositol-3-kinase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLIOMA CELL PROLIFERATION MEDIATED BY COENZYME Q10 AT SERUM DEPRIVATION IN VITRO. Krylova, NG., Kulahova, TA., Koren, SV., et al.[2018]

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“We are excited to present the latest data from the BPM31510 GBM phase 2 trial at the ESMO Congress,” said Dr. Seema Nagpal, Clinical Professor ...

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In this review, we highlight the importance of genomic and proteomic research on identifying novel biomarkers and drug targets for GBM treatment. Additionally, ...

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BPM31510 + Vitamin K1 for Glioblastoma

Research shows that BPM31510, which delivers high levels of ubidecarenone (a form of CoQ10), can selectively target and kill glioblastoma cells by exploiting ...

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This phase I trial studies the side effects and best dose of ubidecarenone injectable nanosuspension (BPM31510) in treating patients with high-grade glioma ...

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BP31510 (Ubidecarenone,USP) Nanosuspension for ...

This is a Phase 1a/b multicenter, open-label, non-randomized, dose-escalation study to examine the dose limiting toxicities (DLT) of BPM31510.