Dichloroacetate for Glioblastoma

(DCA Trial)

Overseen By Peter Stacpoole, Phd, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Insulin, Sulfonylureas

Disqualifiers: Pregnancy, Uncontrolled illness, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if dichloroacetate (DCA) can effectively target glioblastoma, a type of brain tumor, by disrupting the cancer cells' energy production. Participants will receive DCA either before or after surgery to remove the tumor, allowing researchers to compare its effects. Individuals with recurrent or worsening glioblastoma, experiencing symptoms like headaches or seizures, might be suitable candidates. The goal is to assess whether DCA can make cancer cells more vulnerable to treatment, potentially improving outcomes. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You can continue taking your current medications for other conditions, like high blood pressure or seizures, but if you need insulin or sulfonylurea therapy, you won't be eligible for the trial.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

A previous study found that dichloroacetate (DCA) was well-tolerated by patients with brain tumors, including glioblastomas. Research has shown that oral DCA is generally safe. Some studies highlight that the main side effect, nerve damage, can be reversed and managed by adjusting the dose. Another study found that DCA can be used safely if the dose is customized for each person to avoid side effects. Overall, DCA appears safe for humans, especially when doses are personalized to reduce risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Unlike the standard treatments for glioblastoma, such as surgery, radiation, and chemotherapy, Dichloroacetate (DCA) targets the metabolic processes of cancer cells. Most treatments attack the tumor directly, but DCA works differently by altering the way cancer cells process energy, potentially making them more vulnerable to other treatments. Researchers are particularly excited about DCA because it could enhance the effectiveness of surgery and other therapies by weakening the tumor cells before and after removal, offering a novel approach in tackling this aggressive form of brain cancer.

What evidence suggests that Dichloroacetate might be an effective treatment for glioblastoma?

Research shows that dichloroacetate (DCA) might help treat glioblastoma, a type of brain cancer. Studies indicate that DCA can cross the blood-brain barrier, allowing it to target the tumor directly. It restores normal energy production in cells, which may lead to cancer cell death. Previous research suggests that DCA is generally safe and well-tolerated by patients with brain tumors. Some studies also indicate that DCA can enhance the effectiveness of other cancer treatments by stressing cancer cells. In this trial, participants will be divided into two groups: one group will receive pre-surgical dosing of DCA, while the other will not. Both groups will receive post-surgical DCA dosing based on individual drug metabolism rates. Overall, DCA appears promising as a treatment for glioblastoma, but more research is needed to confirm its effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Stuart Grossman, MD

Principal Investigator

Johns Hopkins/ABTCv2

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Patients must be able to provide written informed consent

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

I can swallow liquids without difficulty.

Exclusion Criteria

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

I have recovered from previous cancer treatment side effects, except for hair loss.

Patients receiving any other investigational agents for brain tumor are ineligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical Treatment

Dichloroacetate (DCA) is administered orally twice daily for 7 days prior to scheduled surgery

1 week

Daily dosing

Surgery and Recovery

Participants undergo tumor debulking surgery and recover from the procedure

2-4 weeks

Post-surgical Treatment

DCA is administered twice daily continuously for each 60-day cycle

60 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 2 months

Clinic visits every 2 months with standard of care brain imaging and laboratory studies

What Are the Treatments Tested in This Trial?

Interventions

• Dichloroacetate

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm 2 - NO Pre-surgical dosing Experimental Treatment 1 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 dosing Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Published Research Related to This Trial

Intravenous (IV) administration of dichloroacetate sodium (DCA) has shown safety in high doses (up to 100 mg/kg/dose) for both healthy volunteers and critically ill patients, making it a promising option for cancer treatment.

In three cases of patients with recurrent cancers who had failed conventional therapies, IV DCA treatment resulted in clinical, hematological, or radiological responses, suggesting potential efficacy in advanced-stage cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel form of dichloroacetate therapy for patients with advanced cancer: a report of 3 cases. Khan, A., Marier, D., Marsden, E., et al.[2019]

Sodium dichloroacetate (DCA) has shown the ability to induce programmed cell death in various cancer cells and can also act as a cytostatic agent, stabilizing disease without necessarily causing cell death.

A case study of a 32-year-old male with recurrent metastatic melanoma demonstrated that DCA therapy led to regression and stabilization of the disease for over 4 years with minimal side effects, suggesting its potential as a long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term stabilization of metastatic melanoma with sodium dichloroacetate. Khan, A., Andrews, D., Shainhouse, J., et al.[2020]

Dichloroacetate (DCA) treatment in cancer cells leads to increased autophagy and production of reactive oxygen species (ROS), along with inhibition of the mTOR pathway, which is important for cell growth and metabolism.

After stopping DCA treatment, the metabolic changes, such as lactate excretion and NAD(+)/NADH ratios, returned to normal levels, indicating that the effects of DCA are reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dichloroacetate induces autophagy in colorectal cancer cells and tumours. Lin, G., Hill, DK., Andrejeva, G., et al.[2022]

Dichloroacetate (DCA) selectively induced apoptosis in pediatric tumor cells but only moderately inhibited growth across 18 different tumor cell lines, suggesting limited efficacy as a standalone treatment.

DCA was found to reduce the effectiveness of cisplatin and doxorubicin in several cell lines, indicating that its use in combination with standard chemotherapy drugs may require careful evaluation to avoid compromising treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs. Heshe, D., Hoogestraat, S., Brauckmann, C., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4455946/

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent ... Chronic, oral DCA is feasible and well-tolerated in patients with recurrent malignant gliomas and other tumors metastatic to the brain.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00540176

The Safety and Efficacy of DCA for the Treatment of Brain ... Therefore we hypothesize that DCA will be an effective and relative non-toxic potential therapy for malignant gliomas. We are conducting a phase II trial with 2 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0891584924011547

Nonthermal plasma boosted dichloroacetate induces ... The combination of dichloroacetate (DCA) and nonthermal plasma induces oxidative stress, enhancing glioblastoma stem cell (GSC) based therapy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7923996/

The Effectiveness of Dichloroacetate on Human Glioblastoma ... The data indicate that U87 and PBT24 tumors show different sensitivity to treatment with the sodium salt of dichloroacetate (Figures 1 and 2). A ...

5. elischolar.library.yale.edu elischolar.library.yale.edu/cgi/viewcontent.cgi?article=1152&context=ysmpa_theses

Dichloroacetate as a Metabolic Treatment for Glioblastoma The primary outcome for the proposed study is overall survival, which is defined as date of randomization until death. Data from patients who ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01111097

Study of the Safety and Efficacy of Dichloroacetate (DCA) ... 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).

7. anticancerfund.org anticancerfund.org/en/trials/study-safety-and-efficacy-dichloroacetate-glioblastoma-and-other-recurrent-brain-tumours

Glioblastoma and other recurrent brain tumours Results, published here, showed that DCA can be used safely in patients with RMBT but individualisation of the dose of DCA is required to avoid side effects.

8. reporter.nih.gov reporter.nih.gov/search/XWKIYN8gS0az_VFDL4EIzA/project-details/10281354

Phase IIA Trial of Dichloroacetate for Glioblastoma ... ... DCA may be a safe and uniquely effective metabolic therapy for GBM. DCA inhibits its own metabolism and its only clinically limiting toxicity is reversible ...