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

September 18, 2015 updated by: University of Florida

Phase 1, Open-Label, Single-Arm, Clinical and Metabolomics Study of Dichloroacetate (DCA) in Adults With Recurrent Malignant Brain Tumors

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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 88 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cohort 1
Subjects are given a dose of Dichloroacetate 4mg/kg twice a day for 30 days
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 Names:
  • DCA
Active Comparator: Cohort 2
Subjects are given a dose of Dichloroacetate 12.5mg/kg twice a day for 30 days
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 Names:
  • DCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the safety and tolerability of DCA in RMBTs.
Time Frame: Within 28 days of starting DCA +/- 3 days
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.
Within 28 days of starting DCA +/- 3 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Conduct an exploratory investigation of the metabolites of patients with RMBTs and the effects of DCA thereon.
Time Frame: One year
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.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Erin M. Dunbar, MD, University of Florida
  • Study Chair: Peter W. Stacpoole, PhD, MD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

April 23, 2010

First Submitted That Met QC Criteria

April 26, 2010

First Posted (Estimate)

April 27, 2010

Study Record Updates

Last Update Posted (Estimate)

September 22, 2015

Last Update Submitted That Met QC Criteria

September 18, 2015

Last Verified

September 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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