DCA for Glioblastoma

Recruiting at 4 trial locations

Overseen By Tom Franklin, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Insulin, Sulfonylureas

Disqualifiers: Pregnancy, End stage renal failure, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if DCA, a medication taken by mouth, can help treat patients with returning brain tumors who are scheduled for surgery. DCA may change how tumor cells use energy, potentially slowing their growth. DCA has shown potential activity against several human cancers, including brain tumors.

Will I have to stop taking my current medications?

You can keep taking your current medications, except if you need insulin or sulfonylurea for diabetes. If you use these, you cannot join the trial.

Is DCA generally safe for humans?

DCA has been studied for safety in humans, showing some dose-related, reversible side effects like nerve damage (neurotoxicity) when taken orally. However, high-dose intravenous DCA has been confirmed as safe in both healthy and critically ill patients, with no systemic toxic effects observed in animal studies. ^{1 2 3 4 5}

What makes the drug DCA unique for treating glioblastoma?

DCA is unique because it can cross the blood-brain barrier and targets mitochondria in cancer cells, helping to stop tumor growth and induce cancer cell death. This is different from many other treatments that may not effectively reach brain tumors or work through this specific mechanism. ^{1 3 4 6 7}

What data supports the effectiveness of the drug DCA for treating glioblastoma?

Research shows that DCA can penetrate the blood-brain barrier and has potential antitumor effects on brain tumors, including gliomas, by inhibiting cell growth and inducing cell death. Additionally, DCA has shown effectiveness in stabilizing other types of cancer, such as melanoma, suggesting it may help manage tumor growth. ^{1 3 4 8 9}

Research Team

Peter Stacpoole, PhD, MD

Principal Investigator

University of Florida

Eligibility Criteria

Adults aged 18-80 with recurrent Glioblastoma Multiforme (GBM) who have already undergone surgery, radiation, and chemotherapy with temozolomide are eligible. They must not be pre-terminal or pregnant, nor can they have severe liver insufficiency, end-stage renal failure, or be on insulin/sulfonylurea therapy for diabetes.

Inclusion Criteria

I've had surgery, radiation, and TMZ for my cancer but it didn't work. If my GBM is unmethylated, I haven't had TMZ.

I am being treated at Johns Hopkins or Wake Forest University and can take my current medications, except insulin or sulfonylureas.

I am not at risk for drug interactions with DCA based on its unique metabolism and past trial data.

Exclusion Criteria

Patients considered pre-terminal (life expectancy ≤ 2 months)

Patients with Hgb A1c level less than 6.0 at screening

Those who are pregnant will be excluded

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgical Treatment

Participants receive DCA or no DCA for one week prior to surgery

1 week

Surgery

Participants undergo clinically indicated debulking surgery

1 day

Post-Surgical Treatment

Participants start DCA 12-24 hours postoperatively, depending on their ability to safely receive medication

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dichloroacetate (DCA)

Trial Overview The trial is testing oral Dichloroacetate (DCA) in patients with GBM to establish safe dosing based on genotyping. Participants will either receive DCA or no treatment for one week before their clinically indicated tumor removal surgery.

Participant Groups

Group I: No Pre-Surgical Dichloroacetate (DCA) Active Control 2 Interventions

Subject randomized to start DCA after surgery will do so 12-24 hours postoperatively, depending on their ability to safely receive medication.

Group II: Pre-Surgical Dichloroacetate (DCA) Active Control 2 Interventions

Study medication begins in subjects randomized to preoperative DCA. All subjects will be given the 12.5 mg/kg/12 hour DCA for pre-surgical dosing. Post-surgery the GSTZ1 haplotype will be utilized to dose all patients.

Dichloroacetate (DCA) is already approved in Canada for the following indications:

Approved in Canada as Dichloroacetic acid for:

• Topical treatment of warts
• Cauterization and removal of skin and tissue lesions

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Findings from Research

Dichloroacetate (DCA) effectively inhibits the growth of C6 glioma cells by inducing apoptosis and arresting the cells in the S phase, demonstrating its potential as a treatment for brain tumors.

In animal models, DCA significantly reduced tumor growth in C6 glioma-bearing rats and mice, while also increasing reactive oxygen species (ROS) production and exhibiting antiangiogenic effects, suggesting a multifaceted mechanism of action against gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation. Duan, Y., Zhao, X., Ren, W., et al.[2021]

Sodium dichloroacetate (DCA) effectively reduces the viability of various leukemia cell lines, with sensitivity varying by cell type; CEM/C1 cells were most sensitive (IC50 of 30 mM) while HL-60/MX2 cells were most resistant (IC50 of 75 mM).

DCA treatment alters gene expression profiles related to apoptosis in leukemia cells, but does not activate a specific apoptosis pathway, indicating that further research is needed to understand the molecular mechanisms behind DCA's anticancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium dichloroacetate on apoptotic gene expression in human leukemia cell lines. Abramek, J., Bogucki, J., Ziaja-Sołtys, M., et al.[2020]

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]

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]

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]

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) effectively reduces the viability of B16-F10 melanoma cells in vitro, with significant effects observed at concentrations of 10, 20, and 50 mM after 24 to 72 hours of treatment.

In vivo studies in mice showed that DCA significantly reduced tumor growth at all tested doses (25, 75, and 150 mg/kg) over 10 days, without causing systemic toxicity or affecting body weight, suggesting its potential as a repurposed treatment for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium dichloroacetate attenuates the growth of B16-F10 melanoma in vitro and in vivo: an opportunity for drug repurposing. do Nascimento, RS., Nagamine, MK., De Toledo, GF., et al.[2021]

Dichloroacetate sodium (DCA) has been found to promote cancer cell death through a novel mechanism, leading to its off-label use in cancer treatment.

In a case report involving a 71-year-old male with metastatic cancer, DCA provided significant relief from leg pain after conventional therapies were ineffective, suggesting its potential as a palliative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of oral dichloroacetate for palliation of leg pain arising from metastatic poorly differentiated carcinoma: a case report. Khan, A.[2021]

Dichloroacetate (DCA) effectively reduces the survival of MCA fibrosarcoma cells in a dose-dependent manner, enhancing cancer cell cytotoxicity, especially when combined with mouse splenocytes, which lowers the effective dose needed for inhibition.

DCA modulates the immune response by significantly increasing IL-12 production from macrophages, which in turn enhances IFN-γ levels, indicating its potential as an immunomodulatory agent in cancer treatment through the IL-12-IFN-γ pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dichloroacetate modulates cytokines toward T helper 1 function via induction of the interleukin-12-interferon-γ pathway. Badr, MM., Qinna, NA., Qadan, F., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of sodium dichloroacetate on apoptotic gene expression in human leukemia cell lines. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Dichloroacetate induces autophagy in colorectal cancer cells and tumours. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term stabilization of metastatic melanoma with sodium dichloroacetate. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

A novel form of dichloroacetate therapy for patients with advanced cancer: a report of 3 cases. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Sodium dichloroacetate attenuates the growth of B16-F10 melanoma in vitro and in vivo: an opportunity for drug repurposing. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Use of oral dichloroacetate for palliation of leg pain arising from metastatic poorly differentiated carcinoma: a case report. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Dichloroacetate modulates cytokines toward T helper 1 function via induction of the interleukin-12-interferon-γ pathway. [2021]