Study of the Safety and Efficacy of Dichloroacetate (DCA) in Glioblastoma and Other Recurrent Brain Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01111097
First received: April 23, 2010
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Brain Tumor
Glioblastoma
Drug: Dichloroacetate
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1, Open-Label, Single-Arm, Clinical and Metabolomics Study of Dichloroacetate (DCA) in Adults With Recurrent Malignant Brain Tumors

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Determine the safety and tolerability of DCA in RMBTs. [ Time Frame: Within 28 days of starting DCA +/- 3 days ] [ Designated as safety issue: Yes ]
    Oral DCA will be administered until intolerance, toxicity, radiographic progression, or death. Safety and tolerance will be assessed by reviewing available standardized clinical, radiographic, and quality of life (QOL) criteria. The safety and tolerance will also be assessed by reviewing available plasma, urine, and brain tumor tissue for metabolites of the tumor and the effects of DCA thereon.


Secondary Outcome Measures:
  • Conduct an exploratory investigation of the metabolites of patients with RMBTs and the effects of DCA thereon. [ Time Frame: One year ] [ Designated as safety issue: No ]
    We postulate that the metabolism of RMBTs and the effects of DCA thereon will help investigators understand RMBTs, how DCA works on them, and how to design future treatment studies.


Enrollment: 15
Study Start Date: April 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cohort 1
Subjects are given a dose of Dichloroacetate 4mg/kg twice a day for 30 days
Drug: Dichloroacetate
Subjects after passing the inclusion criteria are given a dose of dichloroacetate 4mg/kg bid for thirty days. While in the clinical research center they participate in a breath test where they exhale through a straw into a glass tube. This will measure CO2. They are monitored every two weeks for side effects and return to the clinical research center for evaluation in thirty days. They undergo another breath test and if all health parameters are within normal limits they are given a month's supply of dichloroacetate. The cycles continue unless a serious adverse event occurs or the PI judges the side effects preclude another 30 days of medication
Other Name: DCA
Active Comparator: Cohort 2
Subjects are given a dose of Dichloroacetate 12.5mg/kg twice a day for 30 days
Drug: Dichloroacetate
Subjects after passing the inclusion criteria are given a dose of dichloroacetate 4mg/kg bid for thirty days. While in the clinical research center they participate in a breath test where they exhale through a straw into a glass tube. This will measure CO2. They are monitored every two weeks for side effects and return to the clinical research center for evaluation in thirty days. They undergo another breath test and if all health parameters are within normal limits they are given a month's supply of dichloroacetate. The cycles continue unless a serious adverse event occurs or the PI judges the side effects preclude another 30 days of medication
Other Name: DCA

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

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111097

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Erin M. Dunbar, MD University of Florida
Study Chair: Peter W. Stacpoole, PhD, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01111097     History of Changes
Other Study ID Numbers: 99-2010, CTSI
Study First Received: April 23, 2010
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Brain tumors, Glioblastoma and DCA
Brain tumor,Glioblastoma recurrent

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on July 22, 2014