Clinical trial NCT01111097: Study of the Safety and Efficacy of Dichloroacetate (DCA) in Glioblastoma and Other Recurrent Brain Tumors
Official title: Phase 1, Open-Label, Single-Arm, Clinical and Metabolomics Study of Dichloroacetate (DCA) in Adults With Recurrent Malignant Brain Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain Tumor
Glioblastoma
Keywords: Brain tumors, Glioblastoma and DCA
Brain tumor,Glioblastoma recurrent
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2010-04-27
Enrollment: 15
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of oral Dichloroacetate (DCA) in the treatment of recurrent malignant brain tumors (RMBTs). RMBTs are defined as either: 1) malignant tumors, originating in the brain, that have recurred at least once or 2) malignant tumors originating elsewhere in the body that have spread to the brain at least once. Otherwise, there are no limitations to the number of prior recurrences. There are no limitations to the number or types of prior therapies.

Detailed description: Malignant brain tumors are defined as any World Health Organization grade III-IV glioma and any solid tumor metastasis (spread) to the brain. Recurrent malignant brain tumors (RMBTs) are defined as either: 1) malignant tumors, originating in the brain, that have recurred at least once or 2) malignant tumors originating elsewhere in the body that have spread to the brain at least once. They share an increasing incidence, clinical and radiographic characteristics, lack of effective therapies, tendency to recur, and poor outcome. Importantly, recurrent malignant brain tumor's shared characteristics may be usefully exploited by an emerging class of biologic agents called metabolic modulators of which Dichloroacetate (DCA) is the drug in the class most thoroughly investigated clinically. DCA's mechanism of action and tolerability have been extensively demonstrated in the treatment of chronic metabolic disorders. Furthermore, the preciseness of DCA's mechanism of action appears to target abnormal tumor cell metabolism.

Eligibility criteria: Inclusion Criteria:

* Subject must be able to consent for self. Subject must have either:

  1. a brain metastasis or
  2. a WHO III-IV glioma that has recurred at least once. Females of child bearing age must have (-) pregnancy test.
* Females of child bearing age must use birth control while in study.
* Adequate organ function as determined by laboratory testing.
* Absence of peripheral neuropathy of moderate or greater severity (physician determined).
* Greater than 4 weeks time from previous anti-neoplastic (anti-cancer) therapy.
* Subject must have a Karnofsky Performance Status (KPS) of greater than or equal to 60.
* Subject must have an ECOG performance status of less than or equal to 2.
* There are no limitations to the number of prior recurrences.
* There are no limitations to the number or types of prior therapies.

Exclusion Criteria:

* Medical contraindication for magnetic resonance imaging (MRI)testing.

Primary outcomes:
measure: Determine the safety and tolerability of DCA in RMBTs.
timeFrame: Within 28 days of starting DCA +/- 3 days
Secondary outcomes:
measure: Conduct an exploratory investigation of the metabolites of patients with RMBTs and the effects of DCA thereon.
timeFrame: One year
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Erin M. Dunbar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Peter W. Stacpoole, PhD, MD
role: STUDY_CHAIR
References:
citation: Dunbar EM, Coats BS, Shroads AL, Langaee T, Lew A, Forder JR, Shuster JJ, Wagner DA, Stacpoole PW. Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors. Invest New Drugs. 2014 Jun;32(3):452-64. doi: 10.1007/s10637-013-0047-4. Epub 2013 Dec 3.