Gallium Maltolate for Glioblastoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Medical College of Wisconsin
Must not be taking: Cytotoxic chemotherapy, Iron supplements
Disqualifiers: Active malignancy, Severe heart disease, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
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.12345
Research Team
Jennifer M. Connelly
Principal Investigator
Medical College of Wisconsin
Eligibility Criteria
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 18 years old or older.
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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
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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.
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Trial Timeline
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
Treatment Details
Interventions
- Gallium maltolate (Metal Complex)
Trial OverviewThe 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.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Dose-expansion PhaseExperimental Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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 Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Froedtert Hospital & the Medical College of WisconsinMilwaukee, WI
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Who Is Running the Clinical Trial?
Medical College of Wisconsin
Lead Sponsor
Trials
645
Patients Recruited
1,180,000+
Findings from Research
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]
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]
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]
References
Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels. [2013]
Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma. [2020]
Increased cure rate of glioblastoma using concurrent therapy with radiotherapy and arsenic trioxide. [2018]
Role of antioxidant enzyme expression in the selective cytotoxic response of glioma cells to gamma-linolenic acid supplementation. [2019]
A rapid assay for drug sensitivity of glioblastoma stem cells. [2016]