Gallium Maltolate for Glioblastoma

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical College of Wisconsin

Must not be taking: Cytotoxic chemotherapy, Iron supplements

Disqualifiers: Active malignancy, Severe heart disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called gallium maltolate (Gallixa) to assess its safety and effect on glioblastoma, an aggressive brain cancer that has returned after treatment. The study aims to determine the safe dosage for participants. Individuals who have had glioblastoma and completed standard treatments like radiation and chemotherapy, yet still experience cancer recurrence, might be suitable for this study. Participants will receive varying doses of the drug to identify the safest and most effective amount. 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 drug.

Will I have to stop taking my current medications?

Participants must stop taking oral iron supplements or iron chelators at least one week before starting the trial medication. The protocol does not specify other medication restrictions, but concurrent use of cytotoxic chemotherapy is not allowed.

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

Research has shown that gallium maltolate (GaM) is generally well-tolerated by patients with relapsed glioblastoma, a type of brain cancer. In ongoing studies, adults have taken GaM without significant side effects, suggesting it is generally safe. The studies reported no major negative reactions, highlighting its promising safety. However, as it is still being tested in an early phase 1 trial, more information is needed to fully confirm these findings. ^{1 2 3 4 5}

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

Unlike the standard treatments for glioblastoma, which usually involve surgery, radiation, and chemotherapy, gallium maltolate offers a unique approach by using gallium, a metal that can interfere with cancer cell growth. Researchers are excited about gallium maltolate because it targets iron metabolism in cancer cells, potentially slowing tumor growth in a way that traditional therapies don't. This new mechanism of action could provide an alternative for patients who are not responding well to current treatments.

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

Research has shown that gallium maltolate (GaM) can slow the growth of glioblastoma, a type of brain cancer, and extend survival in animal studies. In earlier research, patients treated with GaM lived about 14 months on average after starting treatment, which is encouraging for those with recurrent glioblastoma. GaM mimics iron, which cancer cells need to grow, thereby starving the tumor. The FDA has recognized its potential by granting it orphan drug status for glioblastoma, highlighting its promise as a treatment option. This trial will explore various dose levels of GaM to determine the maximum-tolerated dose and further assess its effectiveness, offering hope for those battling this aggressive cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Jennifer M. Connelly

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults diagnosed with relapsed glioblastoma who've completed standard treatments, including radiotherapy and temozolomide. They must have measurable disease or confirmed recurrence, be in fair health (ECOG 0-2), and have proper organ function. Women of childbearing potential and men must agree to contraception methods.

Inclusion Criteria

I am a woman who is either postmenopausal, surgically sterile, using contraception, or practicing true abstinence.

Voluntary written consent must be obtained before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

I am a man and will use effective contraception or practice abstinence.

Exclusion Criteria

I cannot swallow or keep pills down.

Known hypersensitivity to or intolerance to gallium-based medications.

I haven't finished all recommended treatments like surgery or radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive oral gallium maltolate in a 3 + 3 dose-escalation design to determine the maximum-tolerated dose

28 days per cohort

Regular visits for dose-limiting toxicity assessment

Dose-expansion

A minimum of six participants will be enrolled at the recommended phase 2 dose to further assess safety and efficacy

6 months

Imaging every 8 weeks

Follow-up

Participants are monitored for progression-free survival and overall survival

6 months

Imaging every 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gallium maltolate

Trial Overview The trial is testing different doses of oral gallium maltolate for safety and initial effectiveness in treating recurrent glioblastoma. Participants will receive one of several dose levels, including a recommended phase 2 dose determined during the study.

How Is the Trial Designed?

Group I: Dose-expansion Phase Experimental Treatment 1 Intervention

A minimum of six participants will be enrolled in the dose expansion phase for a total of 12 subjects at the recommended phase 2 dose.

Group II: Dose-escalation Phase (500 mg) Experimental Treatment 1 Intervention

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Group III: Dose-escalation Phase (2,500 mg) Experimental Treatment 1 Intervention

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Group IV: Dose-escalation Phase (2,000 mg) Experimental Treatment 1 Intervention

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Group V: Dose-escalation Phase (1,500 mg) Experimental Treatment 1 Intervention

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Group VI: Dose-escalation Phase (1,000 mg) Experimental Treatment 1 Intervention

This is a 3 + 3 design. Participants will be entered sequentially. If 0 of 3 participants has a dose-limiting toxicity (DLT), new participants may be entered at the next higher dose level. If 1 of 3 participants has a DLT, up to 3 more participants are to be treated at that same dose level. If 0 of the additional 3 participants at that dose level has a DLT, new participants may be entered at the next higher dose level. If 1 or more of the additional 3 participants experience a DLT, 0 participants are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the dosed participants has a DLT on the first dose level, the drug will be administered at a lower dose. If 0 of 3 participants has a DLT at the highest dose level, an additional 3 participants will be enrolled to ensure that 6 participants are treated at the MTD. The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a DLT.

Gallium maltolate is already approved in United States for the following indications:

Approved in United States as Gallium maltolate for:

• Orphan drug designation for pediatric and adult glioblastoma multiforme

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

GLA (gamma-linolenic acid) supplementation increases the polyunsaturated fatty acid (PUFA) content in both glioma and normal astrocyte cells, but glioma cells show a greater increase, which may contribute to their cytotoxicity.

The cytotoxic effect of GLA on glioma cells is linked to their higher catalase (CAT) activity compared to normal astrocytes, suggesting that glioma cells cannot effectively upregulate CAT in response to GLA, leading to increased susceptibility to its effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of antioxidant enzyme expression in the selective cytotoxic response of glioma cells to gamma-linolenic acid supplementation. Preuss, M., Girnun, GD., Darby, CJ., et al.[2019]

Arsenic trioxide (ATO) significantly enhances the effectiveness of radiation therapy (RT) in killing glioblastoma multiforme (GBM) cells, with a notable increase in cell death observed when ATO is administered shortly before or after RT.

In a preclinical study involving nude mice with established GBM tumors, the combination of ATO and RT led to complete tumor regression in 4 out of 5 mice, demonstrating a promising therapeutic strategy without evident toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased cure rate of glioblastoma using concurrent therapy with radiotherapy and arsenic trioxide. Ning, S., Knox, SJ.[2018]

Low concentrations of gamma-linolenic acid (GLA) (<100 microM) can paradoxically increase glioma cell growth and invasion, which poses a potential risk in treating malignant gliomas.

In contrast, high doses of GLA (>100 microM) effectively impair glioma cell growth, suggesting that local delivery of higher concentrations could be a promising strategy to reduce tumor size while maintaining low toxicity to normal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels. Bell, HS., Wharton, SB., Leaver, HA., et al.[2013]

In a phase II study involving 40 patients with recurrent glioblastoma, ortataxel did not show significant activity in improving progression-free survival at 6 months, with only 11.4% of patients remaining progression-free.

The treatment was associated with notable toxicities, including neutropenia (13.2%) and leukopenia (15.8%), indicating that while some patients experienced prolonged benefits, the overall efficacy was limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. Silvani, A., De Simone, I., Fregoni, V., et al.[2020]

A new rapid assay was developed to test the effects of various drugs on glioblastoma stem cells, using only 20,000 CD133+ cells to form neurospheres in just 1-2 days.

The assay demonstrated that certain drugs, including Gleevec and DAPT, can effectively disperse neurospheres and induce cell death at low concentrations, with drug combinations showing enhanced effects, indicating potential for personalized treatment strategies in GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rapid assay for drug sensitivity of glioblastoma stem cells. Gal, H., Makovitzki, A., Amariglio, N., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10822938/

Potent in vivo efficacy of oral gallium maltolate in treatment ... Monotherapy with the iron-mimetic GaM profoundly inhibits trGBM growth and significantly extends disease-specific survival in vivo.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04319276

NCT04319276 | Oral Gallium Maltolate for the Treatment of ... This is a phase 1 investigational study to assess the safety and preliminary efficacy of oral gallium maltolate (GaM) in participants with relapsed glioblastoma ...

3. glioblastomamultiforme.it glioblastomamultiforme.it/en/research-news-in-the-second-two-months-of-2025/

Research News in the Second Two-months of 2025 Among the 23 evaluable patients treated daily with GaM, the average overall survival was about 14 months from the start of therapy, a positive ...

4. onclive.com onclive.com/view/fda-awards-orphan-drug-designation-to-gallium-maltolate-for-pediatric-glioblastoma-multiforme

FDA Awards Orphan Drug Designation to Gallium ... The FDA has granted an orphan drug designation to gallium maltolate for use as a potential therapeutic option in pediatric patients with glioblastoma ...

5. biorxiv.org biorxiv.org/content/10.1101/2025.09.17.676610v1.full.pdf

Title: Culture Dimensionality Governs Gallium Maltolate ... The proven effectiveness of GaM against treatment- resistant cells provides strong prospects for developing an effective therapy for aggressive ...

6. academic.oup.com academic.oup.com/neuro-onc-peds/article/1/Supplement_1/wuaf001.100/8231139

A Phase 1 Clinical Trial of Gallium Maltolate for the Treatment ... In our ongoing Phase 1 trial of oral GaM for adult patients with recurrent glioblastoma, GaM has been well-tolerated without significant side ...

7. endbraincancer.org endbraincancer.org/2025/01/expanded-access-to-gallium-maltolate-gam/

Expanded Access to Gallium Maltolate (GaM) Oral GaM has shown an impressive safety profile. Learn More. Sponsored by Imaging Biometrics, this program was set up specifically for patients ...