Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)
NCT ID: NCT05120284
Last Updated: 2025-08-29
Study Results
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Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
40 participants
INTERVENTIONAL
2022-07-01
2026-08-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pre-Surgical Dichloroacetate (DCA)
Study medication begins in subjects randomized to preoperative DCA. All subjects will be given the 12.5 mg/kg/12 hour DCA for pre-surgical dosing. Post-surgery the GSTZ1 haplotype will be utilized to dose all patients.
Dichloroacetate (DCA)
Study medication DCA is a liquid formulation mixed with an artificial sweetener containing aspartame and strawberry extract (50mg/mL)
Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens:
EGT carriers will receive 12-14 mg/kg/12hr DCA. EGT non-carriers will receive 6-7 mg/kg/12 hr.
Genotype
Participants will be genotyped to determine GSTZ1 haplotype status.
No Pre-Surgical Dichloroacetate (DCA)
Subject randomized to start DCA after surgery will do so 12-24 hours postoperatively, depending on their ability to safely receive medication.
Dichloroacetate (DCA)
Study medication DCA is a liquid formulation mixed with an artificial sweetener containing aspartame and strawberry extract (50mg/mL)
Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens:
EGT carriers will receive 12-14 mg/kg/12hr DCA. EGT non-carriers will receive 6-7 mg/kg/12 hr.
Genotype
Participants will be genotyped to determine GSTZ1 haplotype status.
Interventions
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Dichloroacetate (DCA)
Study medication DCA is a liquid formulation mixed with an artificial sweetener containing aspartame and strawberry extract (50mg/mL)
Participants will be genotyped to determine GSTZ1 (glutathione S-transferase Zeta-1) haplotype status, which will stratify this group into 1 of 2 dose regimens:
EGT carriers will receive 12-14 mg/kg/12hr DCA. EGT non-carriers will receive 6-7 mg/kg/12 hr.
Genotype
Participants will be genotyped to determine GSTZ1 haplotype status.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* All subjects will have completed initial, standard- therapy with surgical debulking, followed by radiation and temozolomide (TMZ) and will, therefore, be considered treatment failures. Patients with truly unmethylated GBM do not require prior treatment with temozolomide (TMZ).
* Patients will be recruited and studied at Johns Hopkins University, Johns Hopkins affiliated Sibley Memorial Hospital, and Wake Forest University. The DCA liquid formulation is on file with the FDA, is identical to that administered in our Phase I trial of brain tumor patients and can be given by mouth or feeding tube. Patients may retain whatever medications they are receiving for other conditions (e.g., hypertension, seizures), except patients requiring insulin or sulfonylurea therapy (see below).
* The probability of adverse drug-drug interactions is extremely low, for the following reasons. First, DCA is the only pharmaceutical in clinical use that is metabolized by GSTZ1. Second, DCA is not known to be metabolized by any other drug metabolizing enzyme system, thus precluding competition with other agents for biotransformation. Third, the results of both open label and randomized controlled trials of orally or parenterally administered DCA in the treatment of children and/or adults have never shown evidence of adverse drug-drug interactions (34). Thus, from decades of clinical investigations of use of DCA in various acutely or chronically ill populations, there is nothing to suggest adverse drug-drug interactions should be anticipated in this trial.
* Patients who are diabetic must have a screening hemoglobin A1c (Hgb A1c) level of at least 6.0.
Exclusion Criteria
* Those who are pregnant will be excluded.
* DCA inhibits gluconeogenesis and lowers blood glucose levels in patients with type 2 diabetes. Therefore, in subjects who are receiving either insulin or a sulfonylurea, coadministration of DCA could lead to symptomatic hypoglycemia and those patients will be excluded from the trial.
* DCA is dialyzable and its clearance diminishes in patients with end stage renal failure (GFR ≤ 30 ml/min); such patients will be excluded from participating.
* DCA is metabolized by hepatic GSTZ1, so patients with severe liver insufficiency (total bilirubin \> 2.0 mg/dl or ALT or AST \> 3 x ULN) will be excluded.
* Patients with Hgb A1c level less than 6.0 at screening
18 Years
80 Years
ALL
No
Sponsors
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University of Florida
OTHER
Responsible Party
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Principal Investigators
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Peter Stacpoole, PhD, MD
Role: PRINCIPAL_INVESTIGATOR
University of Florida
Locations
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Wake Forest University
Winston-Salem, North Carolina, United States
Countries
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References
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Other Identifiers
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FD-R-007271-01
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
PRO00034631
Identifier Type: OTHER
Identifier Source: secondary_id
IRB202101509
Identifier Type: -
Identifier Source: org_study_id
NCT05173623
Identifier Type: -
Identifier Source: nct_alias
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