Intra-tumoral MTX110 for Glioblastoma

(MAGIC-G1 Trial)

Recruiting at 1 trial location

Overseen By Nicola Tuckwell

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biodexa Pharmaceuticals

Must not be taking: Chemotherapy, Bevacizumab, Carmustine, Gliadel

Disqualifiers: Re-irradiation, MRI intolerance, Brainstem lesions, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 28 weeks

4 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but you cannot have had chemotherapy or certain other treatments within a few weeks before starting the study drug. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug MTX110 for glioblastoma?

Research shows that panobinostat, a component of MTX110, has anti-cancer effects and has been tested in combination with other drugs for glioblastoma and other tumors, showing potential effectiveness. Additionally, studies in animal models and cell lines suggest panobinostat is active against certain types of brain tumors. ^{1 2 3 4 5}

Is MTX110 (panobinostat) safe for humans?

MTX110 (panobinostat) has been tested in several studies for safety in humans with different types of tumors. Common side effects include thrombocytopenia (low platelet count), which was dose-dependent but resolved quickly. The maximum tolerated dose was identified, and the treatment was generally well-tolerated in the studies. ^{1 2 4 6 7}

What makes the drug MTX110 unique for treating glioblastoma?

MTX110 is unique because it uses a method called convection-enhanced delivery (CED) to directly deliver the drug into the tumor, which helps it bypass the blood-brain barrier that usually prevents drugs from reaching brain tumors. This approach allows for higher concentrations of the drug to reach the tumor site, potentially improving its effectiveness compared to traditional methods. ^{1 2 4 5 8}

What is the purpose of this trial?

This trial tests the safety of MTX110 in patients with recurrent glioblastoma. The drug is delivered directly to the tumor through a catheter to target it more effectively.

Research Team

Gary Shangold

Principal Investigator

Biodexa Pharmaceuticals

Eligibility Criteria

This trial is for patients with recurrent glioblastoma who are healthy enough for surgery and general anesthesia, have a life expectancy over 3 months, and haven't had certain recent treatments. Excluded are those with specific brain lesions, prior nitrosoureas treatment, inability to undergo MRI, or active treatment for another cancer.

Inclusion Criteria

You are expected to live for at least 3 more months.

My brain cancer has come back after treatment.

I am healthy enough to undergo surgery and anesthesia.

Exclusion Criteria

I haven't had chemotherapy or certain cancer drugs in the last 4 weeks.

I am scheduled for or currently receiving a second round of radiation for a returning tumor.

You are unable to have an MRI scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Procedure

Surgical procedure to insert a programmable pump and catheter system for MTX110 administration

1 week

1 visit (in-person)

Treatment

Weekly dosing of MTX110 via CED to assess safety and establish recommended phase 2 dose

28 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MTX110

Trial Overview The study tests the safety of MTX110 when directly administered into the tumor site using a catheter system inserted surgically. The focus is on individuals whose glioblastoma has returned after previous treatments.

Participant Groups

Group I: Cohort B: MTX-110 with optional catheter repositioning Experimental Treatment 2 Interventions

Weekly dosing of MTX110 via CED until progression. At progression, optional catheter repositioning may occur, followed by continued weekly dosing of MTX110 until next progression/ unacceptable toxicity.

Group II: Cohort A: MTX-110 Experimental Treatment 2 Interventions

Weekly dosing of MTX110 via CED until progression/ unacceptable toxicity.

MTX110 is already approved in United States, European Union for the following indications:

Approved in United States as Farydak for:

• Multiple myeloma

Approved in European Union as Farydak for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Biodexa Pharmaceuticals

Lead Sponsor

Trials

2

Recruited

30+

Midatech Ltd

Lead Sponsor

Trials

1

Recruited

4+

Findings from Research

The maximum tolerated dose (MTD) of intravenous panobinostat was determined to be 7.2 mg/m² for daily administration and 20.0 mg/m² for weekly administration in patients with advanced solid tumors or lymphoma, indicating a clear dosing strategy for future studies.

While the intravenous formulation of panobinostat was generally well tolerated, safety concerns such as fatigue, cardiac arrhythmias, and myelosuppressive effects suggest that further development will focus on an oral formulation to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study of intravenous panobinostat in patients with lymphoma and solid tumors. Sharma, S., Beck, J., Mita, M., et al.[2022]

The study determined that the maximum tolerated dose of oral panobinostat is 10 mg taken three times weekly when combined with paclitaxel and carboplatin, with myelosuppression being the main dose-limiting toxicity observed in 21 patients.

Despite significant hematologic toxicities like neutropenia and thrombocytopenia, the treatment showed efficacy with three patients achieving partial responses and eleven others maintaining stable disease, indicating potential benefits for patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors. Jones, SF., Infante, JR., Thompson, DS., et al.[2018]

In a pre-clinical study involving 3 nonhuman primates, the HDAC inhibitor panobinostat showed low penetration into the cerebrospinal fluid (CSF) after oral administration, indicating potential challenges for its effectiveness in treating diffuse intrinsic pontine glioma (DIPG).

Despite being identified as a promising agent against DIPG in previous studies, the low CSF levels of panobinostat suggest that its delivery to the central nervous system may be insufficient, which could limit its therapeutic efficacy in treating this aggressive childhood cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing the pharmacokinetics of panobinostat in a non-human primate model for the treatment of diffuse intrinsic pontine glioma. Rodgers, LT., Lester McCully, CM., Odabas, A., et al.[2021]

The study involved 7 patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) who received a total of 48 infusions of MTX110 via convection-enhanced delivery (CED), showing that this method is tolerable with manageable side effects, primarily transient neurological issues.

The median overall survival for patients was 26.1 months, which is promising compared to historical data for DIPG, suggesting that further research into this treatment strategy is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PNOC015: Repeated convection-enhanced delivery of MTX110 (aqueous panobinostat) in children with newly diagnosed diffuse intrinsic pontine glioma. Mueller, S., Kline, C., Stoller, S., et al.[2023]

In a Phase I study involving 14 Japanese patients with advanced solid tumors, intravenous panobinostat was found to have a maximum tolerated dose (MTD) of 20 mg/m², with dose-limiting toxicity observed in one patient.

While thrombocytopenia (low platelet count) was common and severe in some cases, it resolved quickly, and the treatment showed some antitumor activity with stable disease in six patients for at least four months, although no complete or partial responses were recorded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalating study of panobinostat (LBH589) administered intravenously to Japanese patients with advanced solid tumors. Morita, S., Oizumi, S., Minami, H., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase I dose-escalation study of intravenous panobinostat in patients with lymphoma and solid tumors. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

Characterizing the pharmacokinetics of panobinostat in a non-human primate model for the treatment of diffuse intrinsic pontine glioma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

PNOC015: Repeated convection-enhanced delivery of MTX110 (aqueous panobinostat) in children with newly diagnosed diffuse intrinsic pontine glioma. [2023]

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

Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I dose-escalating study of panobinostat (LBH589) administered intravenously to Japanese patients with advanced solid tumors. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and various degrees of hepatic function. [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model. [2022]