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

NCT ID: NCT01111097

Last Updated: 2015-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2014-03-31

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.

Conditions

Brain Tumor; Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

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

Group Type: ACTIVE_COMPARATOR

Dichloroacetate

Intervention Type: DRUG

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

Cohort 2

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

Group Type: ACTIVE_COMPARATOR

Dichloroacetate

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

DCA

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erin M. Dunbar, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Peter W. Stacpoole, PhD, MD

Role: STUDY_CHAIR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24297161 (View on PubMed)

Other Identifiers

CTSI

Identifier Type: OTHER

Identifier Source: secondary_id

UL1TR000064

Identifier Type: NIH

Identifier Source: secondary_id

View Link

99-2010

Identifier Type: -

Identifier Source: org_study_id