What side effects are associated with this type of intervention?

Common treatments for Glioblastoma include surgery, radiation therapy, and chemotherapy with agents such as temozolomide. Known side effects of these treatments can include fatigue, nausea, vomiting, hair loss, and increased risk of infections due to lowered blood cell counts. For treatments similar to Dichloroacetate (PDK inhibition), potential side effects may include metabolic disturbances, gastrointestinal issues, and neuropathy, as these are common with metabolic modulators. It is important to discuss specific side effects with a healthcare provider, as they can vary based on individual treatment plans.

What prior FDA approvals exist?

The FDA has approved several treatments for glioblastoma, including temozolomide, which is an oral alkylating agent used in combination with radiotherapy and as maintenance therapy. Bevacizumab, an anti-VEGF monoclonal antibody, is also approved for recurrent glioblastoma. While Dichloroacetate (DCA) is being studied for its PDK inhibition properties, there are no current FDA-approved treatments specifically targeting PDK inhibition for glioblastoma. The focus remains on chemotherapeutic agents and targeted therapies like bevacizumab.

What other types of research exist?

Promising novel alternatives to Dichloroacetate (DCA) for Glioblastoma patients include: 1) Tumor Treating Fields (TTFields) - a non-invasive treatment that uses electric fields to disrupt cancer cell division. 2) CAR T-cell therapy - a type of immunotherapy where a patient's T cells are modified to target glioblastoma cells. 3) Oncolytic virus therapy - using genetically modified viruses to selectively infect and kill cancer cells. 4) Targeted therapies such as Bevacizumab (anti-VEGF) and inhibitors targeting specific mutations like EGFRvIII. 5) Combination therapies involving immune checkpoint inhibitors (e.g., Nivolumab) with other agents to enhance anti-tumor response.

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Metabolic Modulator

Dichloroacetate for Glioblastoma (DCA Trial)

Phase 2

Waitlist Available

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have the following organ and marrow function: (1) Absolute neutrophil count >1,500/ µL (2) Platelets ≥100,000/ µL (3) Hemoglobin ≥ 9 g/dL (4) Total bilirubin ≤ 2mg/dl (5) AST (SGOT)/ALT (SGPT) ≤3 × institutional upper limit of normal (6) GFR > 30ml/min

Patients must have histologically confirmed WHO grade IV glioma that is progressive or recurrent following at least one prior TMZ plus radiation therapy regimen

Must not have

Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible

Patients who require insulin or sulfonylurea therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 7 days

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests DCA, a medicine that helps fix cell energy problems, in patients with recurring brain tumors who didn't respond to standard treatments. DCA works by restarting normal cell energy processes to kill cancer cells. DCA has shown activity against several human cancers and has been tested in early research for its potential to treat brain tumors.

Who is the study for?

Adults aged 18-80 with WHO grade IV glioma that's worsening or returning after treatment, able to care for themselves mostly, and not on insulin/sulfonylurea therapy. They must have adequate organ function, be off certain treatments for specific periods, use effective contraception if applicable, and be scheduled for tumor removal surgery.

What is being tested?

The trial is testing Dichloroacetate (DCA), a new type of drug that targets cancer cell metabolism in the brain. It aims to show that DCA can reduce a particular protein in tumors when given before surgery compared to those who don't receive it beforehand.

What are the potential side effects?

While the side effects of DCA are not detailed here, similar drugs may cause issues like nerve damage (neuropathy), fatigue, changes in liver function tests, and possibly affect blood sugar levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My brain tumor has returned or worsened after treatment with TMZ and radiation.

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I have recurring brain cancer with symptoms and surgery planned to remove part of the tumor.

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I have waited the required time after my last cancer treatment before joining this trial.

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I am between 18 and 80 years old.

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I completed most of my planned radiation and chemotherapy for my condition.

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I can take care of myself with some help from others.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any severe illnesses that could interfere with the study.

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I need insulin or sulfonylurea for my diabetes.

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I am not pregnant or breastfeeding if I am to be treated with DCA.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 7 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~7 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 7 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Level of phosphorylated PDC protein expression in tumor tissue

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm 2 - NO Pre-surgical dosingExperimental Treatment1 Intervention

Following recovery from surgical resection*, all patients will receive DCA at the determined individual dosing dose "fast" vs "slow". GSTZ1 haplotype analysis, into "fast" (i.e., EGT carriers; 12.5 mg/kg DCA every 12 hours ± 2hrs) or "slow" (i.e., EGT noncarriers; 6.25 mg/kg DCA every 12 hours ± 2hrs) drug metabolizers Post-surgery (upon recovery, within 2-4 weeks, DCA will be administered twice daily continuously for each 60 day cycle. Each dose should be taken 12 hours apart (±2 hours), at approximately the same times each day.

Group II: Arm 1 - Pre-surgical dosingExperimental Treatment1 Intervention

Dichloroacetate (DCA) will be given orally. Dosing will be 12.5 mg/kg/dose every 12 hours. DCA will be administered twice daily for 7 days prior to scheduled surgery to remove tumor. A final pre-surgical dose should be taken the morning the day before surgery, approximately 12 hours before the surgical procedure begins, i.e. skip evening dose. Following recovery from surgical resection*, all patients will receive DCA at the determined stratification dose "fast" vs "slow". GSTZ1 haplotype analysis, into "fast" (i.e., EGT carriers; 12.5 mg/kg DCA every 12 hours ± 2hrs) or "slow" (i.e., EGT noncarriers; 6.25 mg/kg DCA every 12 hours ± 2hrs) drug metabolizers

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dichloroacetic acid

FDA approved

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Glioblastoma often target the unique metabolic pathways of cancer cells. Dichloroacetate (DCA), for example, inhibits pyruvate dehydrogenase kinase (PDK), which reactivates the pyruvate dehydrogenase complex (PDC). This shifts the cancer cell metabolism from glycolysis to glucose oxidation, increasing mitochondrial activity and inducing selective apoptosis of tumor cells. This approach is significant for Glioblastoma patients as it specifically targets the altered metabolic processes in cancer cells, potentially reducing tumor growth and improving survival rates.