Clincosm LogoSign in Get a demo

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

Sponsor
University of Florida (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05120284
Collaborator
Food and Drug Administration (FDA) (U.S. Fed)
40
Enrollment
1
Location
2
Arms
36
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Conduct a multicenter, open label Phase IIA trial of oral DCA in 40 surgical patients with recurrent GBM who have clinically indicated debulking surgery planned. No patients will be recruited at UF. Patients will be genotyped to establish safe dosing regimens and will be randomized to receive DCA (N=20) or no DCA (N=20) for one week prior to surgery. Deidentified blood and tumor tissue obtained at surgery will be assessed at UF for biochemical markers of DCA dynamics.

Condition or Disease Intervention/Treatment Phase
  • Drug: Dichloroacetate (DCA)
  • Genetic: Genotype
 Phase 2

Detailed Description

Evaluate effects of dichloroacetate (DCA) on tumor PDC phosphorylation.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
subsequent ordered and alternating patientssubsequent ordered and alternating patients
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM)
Anticipated Study Start Date :
Jun 1, 2022
Anticipated Primary Completion Date :
Jun 1, 2025
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Pre-Surgical Dichloroacetate (DCA)

Study medication begins in subjects randomized to preoperative DCA. GSTZ1 haplotype status will stratify subjects into 1 of 2 dose regimens. EGT carriers will receive 12.5 mg/kg/12 hr DCA. EGT noncarriers will receive 6.25 mg/kg/12 hr DCA.

Drug: 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.
Other Names:
  • Sodium Dichloroacetate

    • Genetic: Genotype
    Participants will be genotyped to determine GSTZ1 haplotype status.
    Active Comparator: 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.

    Drug: 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.
    Other Names:
  • Sodium Dichloroacetate

    • Genetic: Genotype
    Participants will be genotyped to determine GSTZ1 haplotype status.

    Outcome Measures

    Primary Outcome Measures

    1. The efficacy will be measured between the groups by using the Observer Reported Outcome (ObsRO) measure of health. [9 months]

      The efficacy of dichloroacetate will be determined by applying a novel Observer Reported Outcome (ObsRO) measure of health. The ObsRO scores will be graded on a Likert Scale from 0-4. (0 being absent and 4 being extremely severe).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 will be recruited and studied at the 11 ABTC clinical sites. 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.

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231

    Sponsors and Collaborators

    • University of Florida
    • Food and Drug Administration (FDA)

    Investigators

    • Principal Investigator: Peter Stacpoole, PhD, MD, University of Florida

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT05120284
    Other Study ID Numbers:
    • IRB202101509
    • FD-R-007271-01
    • PRO00034631
    • NCT05173623
    First Posted:
    Nov 15, 2021
    Last Update Posted:
    May 23, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Glioblastoma

    Study Results

    No Results Posted as of May 23, 2022