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

Primary Purpose

Brain Tumor, Glioblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dichloroacetate
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Tumor focused on measuring Brain tumors, Glioblastoma and DCA, Brain tumor,Glioblastoma recurrent

Eligibility Criteria

21 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Cohort 1

Cohort 2

Arm Description

Subjects are given a dose of Dichloroacetate 4mg/kg twice a day for 30 days

Subjects are given a dose of Dichloroacetate 12.5mg/kg twice a day for 30 days

Outcomes

Primary Outcome Measures

Determine the safety and tolerability of DCA in RMBTs.
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.
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.

Full Information

First Posted
April 23, 2010
Last Updated
September 18, 2015
Sponsor
University of Florida
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT01111097
Brief Title
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

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Tumor, Glioblastoma
Keywords
Brain tumors, Glioblastoma and DCA, Brain tumor,Glioblastoma recurrent

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Active Comparator
Arm Description
Subjects are given a dose of Dichloroacetate 4mg/kg twice a day for 30 days
Arm Title
Cohort 2
Arm Type
Active Comparator
Arm Description
Subjects are given a dose of Dichloroacetate 12.5mg/kg twice a day for 30 days
Intervention Type
Drug
Intervention Name(s)
Dichloroacetate
Other Intervention Name(s)
DCA
Intervention Description
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
Primary Outcome Measure Information:
Title
Determine the safety and tolerability of DCA in RMBTs.
Description
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.
Time Frame
Within 28 days of starting DCA +/- 3 days
Secondary Outcome Measure Information:
Title
Conduct an exploratory investigation of the metabolites of patients with RMBTs and the effects of DCA thereon.
Description
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.
Time Frame
One year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must be able to consent for self. Subject must have either: a brain metastasis or 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erin M. Dunbar, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter W. Stacpoole, PhD, MD
Organizational Affiliation
University of Florida
Official's Role
Study Chair
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24297161
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.
Results Reference
result

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

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