BPM31510 + Vitamin K1 for Glioblastoma

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

50 Participants Needed

Trial Summary

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).

What data supports the effectiveness of the drug BPM31510 + Vitamin K1 for treating glioblastoma?

Research shows that BPM31510, which delivers high levels of ubidecarenone (a form of CoQ10), can selectively target and kill glioblastoma cells by exploiting their vulnerability to oxidative stress. In animal models, this approach led to a significant increase in long-term survival rates, suggesting its potential as an effective treatment for this aggressive brain cancer. ^{1 2 3 4 5}

Is BPM31510 (ubidecarenone) safe for human use?

Ubidecarenone (CoQ10) has been used safely as a dietary supplement and in complementary therapies for heart failure for over two decades, with no reported genotoxic (DNA-damaging) effects in studies. Additionally, CoQ10 formulations have shown no obvious toxicity in lung cell studies, suggesting it is generally safe for human use. ^{1 6 7 8 9}

What makes the drug BPM31510 + Vitamin K1 unique for treating glioblastoma?

BPM31510 delivers high levels of ubidecarenone (a form of Coenzyme Q10) directly to cancer cells, exploiting their vulnerability to oxidative stress, which can selectively kill tumor cells without harming normal cells. This approach is novel because it targets the cancer cells' unique metabolic reprogramming, unlike most treatments that do not differentiate between cancerous and non-cancerous cells. ^{1 2 4 10 11}

What is the purpose of this trial?

This is a single-arm, non-randomized, open-label Phase 2 therapeutic study that will assess the effects of adding BPM31510 onto a conventional treatment framework of RT and concurrent TMZ chemotherapy for subjects with newly diagnosed glioblastoma.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 intramuscular (IM) 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 additional 6 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+

Findings from Research

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]

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]

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]

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]

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]

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, 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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

CoQ10 reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

[The antioxidants (coenzyme Q10) in materno-fetal physiopathology]. [2014]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

GLIOMA CELL PROLIFERATION MEDIATED BY COENZYME Q10 AT SERUM DEPRIVATION IN VITRO. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Improved photostability and cytotoxic effect of coenzyme Q10 by its association with vitamin E acetate in polymeric nanocapsules. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

Genotoxicity studies of ubidecarenone (coenzyme Q10) manufactured by bacteria fermentation. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Evaluation of the mutagenic potential of ubidecarenone using three short-term assays. [2014]

9. England pubmed.ncbi.nlm.nih.gov

Formulation and evaluation of ubidecarenone transdermal delivery systems. [2014]

10. Italy 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. [2013]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma. [2022]