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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01111097
• Other study ID #: 99-2010
• Secondary ID: CTSIUL1TR000064
• Status: Completed
• Phase: Phase 1
• First received: April 23, 2010
• Last updated: September 18, 2015
• Start date: April 2010
• Est. completion date: March 2014

Study information

• Verified date: September 2015
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 90 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor
• Glioblastoma

Intervention

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

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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/s10637-013-004 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Within 28 days of starting DCA +/- 3 days	Yes
Secondary	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.	One year	No