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

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing an oral medicine called gallium maltolate in patients with brain cancer that has come back after treatment. The goal is to see if the medicine can safely stop the growth of cancer cells. Gallium maltolate has shown potential in slowing the growth of glioblastoma by disrupting iron metabolism and inhibiting mitochondrial function.

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.

What makes Gallium maltolate unique for treating glioblastoma?

Gallium maltolate is unique because it is a novel compound that may offer a different mechanism of action compared to traditional treatments like surgery, radiotherapy, and chemotherapy, which have limited effectiveness for glioblastoma. While specific details about its mechanism in glioblastoma are not provided, its use in other conditions suggests it might work differently from existing therapies. ^{1 2 3 4 5}

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

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]

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]

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]

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. United States 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. [2013]

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

Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. [2020]

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

Increased cure rate of glioblastoma using concurrent therapy with radiotherapy and arsenic trioxide. [2018]

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

Role of antioxidant enzyme expression in the selective cytotoxic response of glioma cells to gamma-linolenic acid supplementation. [2019]

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

A rapid assay for drug sensitivity of glioblastoma stem cells. [2016]