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

• ClinicalTrials.gov Identifier: NCT01111097
• Recruitment Status: Completed
• First Posted: April 27, 2010
• Last Update Posted: September 22, 2015
• Sponsor: University of Florida
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): University of Florida

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.

Condition or disease	Intervention/treatment	Phase
Brain Tumor; Glioblastoma	Drug: Dichloroacetate	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: April 2010
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Florida

National Institutes of Health (NIH)

Investigators

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

More Information

Publications of Results:

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.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT01111097
• Other Study ID Numbers: 99-2010; CTSI ( Other Identifier: Ocala Dames ); UL1TR000064 ( U.S. NIH Grant/Contract )
• First Posted: April 27, 2010
• Last Update Posted: September 22, 2015
• Last Verified: September 2015

Keywords provided by University of Florida:

Brain tumors, Glioblastoma and DCA; Brain tumor,Glioblastoma recurrent

Additional relevant MeSH terms:

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