Intra-tumoral MTX110 for Glioblastoma

(MAGIC-G1 Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MTX110 (also known as Panobinostat) for individuals with recurrent glioblastoma, a type of brain cancer that returns after treatment. The main goal is to determine if MTX110 is safe when administered directly to the tumor through a small tube inserted during surgery. Participants will receive weekly doses, and if necessary, the tube can be repositioned to continue treatment. Individuals with recurrent glioblastoma who are healthy enough for surgery might be suitable candidates for this trial. As a Phase 1 trial, the 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 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.

Is there any evidence suggesting that MTX110 is likely to be safe for humans?

Research has shown that MTX110 has been tested in earlier studies with encouraging results. One study on a different type of brain cancer found that patients tolerated repeated doses of MTX110 without severe side effects. Although this study focused on another condition, it suggests that MTX110 might be safe for humans.

Another study on recurrent glioblastoma is examining the safety of MTX110 and its potential to extend patient survival. This ongoing research aims to ensure the treatment does not cause significant harm.

Since this trial is in an early stage, the main goal is to determine if MTX110 is safe for people with recurrent glioblastoma. If proven safe, MTX110 could become a promising treatment option. ^{1 2 3 4 5}

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

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and chemotherapy, MTX110 is unique due to its delivery method and potential mechanism of action. MTX110 is administered directly into the tumor via convection-enhanced delivery (CED), allowing for higher concentrations of the drug to reach the cancer cells with potentially fewer systemic side effects. This targeted approach is hoped to improve outcomes by directly attacking the tumor while minimizing harm to surrounding healthy tissue. Researchers are excited about MTX110 because it could offer a more effective and focused treatment option for glioblastoma, a condition notoriously difficult to treat with current methods.

What evidence suggests that MTX110 might be an effective treatment for glioblastoma?

Research has shown that combining MTX110 with radiation treatment can slow tumor growth by about 50% compared to using either treatment alone. In this trial, participants will receive MTX110 directly to the tumor, reducing side effects in the rest of the body. Studies with patients who have recurrent glioblastoma suggest that MTX110 might extend their survival. Early results indicate that MTX110 effectively targets tumors, making it a promising treatment option. Overall, the evidence is encouraging for those considering MTX110 for recurrent glioblastoma. ^{1 3 5 6 7}

Who Is on the Research Team?

Gary Shangold

Principal Investigator

Biodexa Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8598729/

EXTH-57. EFFICACY OF SOLUBLE PANOBINOSTAT ... MTX110 in combination with radiation treatment showed an enhanced delay in tumor growth of approximately 50% compared to MTX110 or radiation alone.

2. onclive.com onclive.com/view/magic-g1-study-provides-updated-findings-with-mtx110-in-recurrent-glioblastoma

MAGIC-G1 Study Provides Updated Findings With MTX110 ... An update on PFS and OS data from the phase 1 MAGIC-G1 study of MTX110 in recurrent glioblastoma has been released.

3. biodexapharma.com biodexapharma.com/biodexa-provides-update-on-progression-free-and-overall-survival-in-phase-1-study-of-mtx110-in-recurrent-glioblastoma/

Biodexa Provides Update on Progression Free and Overall ... Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for recurrent glioblastoma (NCT05324501) and ...

4. cancernetwork.com cancernetwork.com/view/mtx110-may-show-survival-benefits-in-recurrent-glioblastoma

MTX110 May Show Survival Benefits in Recurrent ... Investigators are assessing the feasibility, safety, and efficacy of MTX110 for patients with recurrent glioblastoma as part of the phase 1 MAGIC-1 study.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X23000193

Efficacy of convection enhanced delivery of MTX110 ... Our results demonstrate that CED of MTX110, has potent antitumor activity with limited systemic toxicity and that hyperpolarized 13 C imaging is able to assess ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37318058/

PNOC015: Repeated convection-enhanced delivery of ... Repeat CED of MTX110 with real-time imaging with gadoteridol is tolerable for patients with DIPG. Median OS of 26.1 months compares favorably with historical ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03566199

Study Details | NCT03566199 | MTX110 by Convection ... Panobinostat nanoparticle formulation MTX110 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Detailed Description.