Using Dichloroacetate to treat recurrent Glioblastoma Multiforme

Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)

This study is testing if a drug called dichloroacetate can help patients with recurrent glioblastoma multiforme feel better before their surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Drugs / interventions: radiation
• Locations: 2 sites (Baltimore, Maryland and 1 other locations)
• Trial ID: NCT05120284 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effects of dichloroacetate (DCA) on patients with recurrent glioblastoma multiforme (GBM) who are scheduled for tumor debulking surgery. It involves a multicenter, open-label Phase IIA design with 40 participants, who will be genotyped to determine safe dosing regimens. Patients will be randomized to receive DCA or a placebo for one week prior to surgery, and their blood and tumor tissue will be analyzed for biochemical markers related to DCA dynamics. The goal is to assess the impact of DCA on tumor phosphorylation dynamics.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with recurrent GBM who have undergone standard treatment and are scheduled for debulking surgery.

Not a fit: Patients with unmethylated GBM who have not undergone prior treatment with temozolomide may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with recurrent GBM, potentially improving outcomes.

How similar studies have performed: While the use of DCA in brain tumors has been explored, this specific approach in recurrent GBM is novel and has not been extensively tested in previous studies.

Eligibility criteria

Inclusion Criteria:

* Study subjects will be male and female adults, aged 18 through 80 years, previously diagnosed with a GBM who have experienced tumor recurrence as determined by neuroimaging and some degree of symptomatology (e.g., headache, mental status change, seizure) and have clinically indicated tumor debulking surgery planned.
* 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:

* Patients considered pre-terminal (life expectancy ≤ 2 months)
* 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

Where this trial is running

Baltimore, Maryland and 1 other locations

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore, Maryland, United States (Recruiting)
• Wake Forest University — Winston-Salem, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Peter Stacpoole, PhD, MD — University of Florida
• Study coordinator: Peter W Stacpoole, PhD, MD

Conditions Glioblastoma Multiforme