DCA for Glioblastoma
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Florida
Must not be taking: Insulin, Sulfonylureas
Disqualifiers: Pregnancy, End stage renal failure, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
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.
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.
12345Is 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.
12467What 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.
12489Eligibility 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.
+2 more
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
+3 more
Trial 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
Participant Groups
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.
2Treatment groups
Active Control
Group I: No Pre-Surgical Dichloroacetate (DCA)Active Control2 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 Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins Bayview Med CtrBaltimore, MD
Sibley Memorial HospitalWashington, United States
University of Alabama - BirminghamBirmingham, AL
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, MD
More Trial Locations
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Who Is Running the Clinical Trial?
University of FloridaLead Sponsor
Food and Drug Administration (FDA)Collaborator
References
Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation. [2021]Dichloroacetate (DCA), a small molecule mitochondria-targeting agent, can penetrate the blood-brain barrier, showing potential therapeutic effects on brain tumors. Considering the effects of DCA on tumor cellular metabolism, penetrating across the blood-brain barrier, as well as having potential antitumor activity on brain tumors, the purpose of this study is to investigate the antitumor activity of DCA on C6 glioma cells in vitro and in vivo. DCA inhibited C6 glioma cell proliferation, induced C6 cell apoptosis, and arrested C6 cells in S phase. DCA can inhibit the expression of heat shock proteins 70 (Hsp70) in a dose-dependent and time-dependent manner (P
Effect of sodium dichloroacetate on apoptotic gene expression in human leukemia cell lines. [2020]Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2.
Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs. [2022]The observation that the orphan drug dichloroacetate (DCA) selectively promotes mitochondria-regulated apoptosis and inhibits tumour growth in preclinical models by shifting the glucose metabolism in cancer cells from anaerobic to aerobic glycolysis attracted not only scientists', clinicians' but also patients' interests and prompted us to further evaluate DCA effects against paediatric malignancies.
Dichloroacetate induces autophagy in colorectal cancer cells and tumours. [2022]Dichloroacetate (DCA) has been found to have antitumour properties.
Long-term stabilization of metastatic melanoma with sodium dichloroacetate. [2020]Sodium dichloroacetate (DCA) has been studied as a metabolic cancer therapy since 2007, based on a publication from Bonnet et al demonstrating that DCA can induce apoptosis (programmed cell death) in human breast, lung and brain cancer cells. Classically, the response of cancer to a medical therapy in human research is measured by Response Evaluation Criterial for Solid Tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging, however disease stabilization is also a beneficial clinical outcome. It has been shown that DCA can function as a cytostatic agent in vitro and in vivo, without causing apoptosis. A case of a 32-year-old male is presented in which DCA therapy, with no concurrent conventional therapy, resulted in regression and stabilization of recurrent metastatic melanoma for over 4 years' duration, with trivial side effects. This case demonstrates that DCA can be used to reduce disease volume and maintain long-term stability in patients with advanced melanoma.
A novel form of dichloroacetate therapy for patients with advanced cancer: a report of 3 cases. [2019]Oral dichloroacetate sodium (DCA) is currently under investigation as a single agent and as an adjuvant for treatment of various cancers. One of the factors limiting its clinical use in a continuous oral regimen is a dose-related, reversible neurotoxicity, including peripheral neuropathy and encephalopathy. The intravenous (IV) route has a number of potential advantages, including (1) pulsed dosing to achieve higher concentrations than feasible with oral use, (2) a longer washout period to reduce the potential for neurotoxicity, and (3) a bypassing of the digestive system, which is particularly significant for advanced-stage cancer patients. Data were available on high-dose IV DCA (up to 100 mg/kg/dose) that have confirmed its safety, both in healthy volunteers and in critically ill patients, allowing the authors to begin off-label treatment of cancer patients. In several of their patients treated with IV DCA, the authors observed clinical, hematological, or radiological responses. This article presents 3 cases with patients who had recurrent cancers and for whom all conventional therapies had failed: (1) a 79-y-old male patient with colon cancer who had liver metastases, (2) a 43-y-old male patient with angiosarcoma who had pancreatic and bone metastases, and (3) a 10-y-old male patient with pancreatic neuroendocrine carcinoma who had liver metastases.
Sodium dichloroacetate attenuates the growth of B16-F10 melanoma in vitro and in vivo: an opportunity for drug repurposing. [2021]Sodium dichloroacetate (DCA) is a metabolic regulator used to treat diabetes. Since DCA inhibits pyruvate dehydrogenase kinase, decreasing lactic acid formation, it can reverse the Warburg effect in cancer cells, promoting apoptosis. Therefore, this study aimed to investigate the potential of DCA as a drug repurposing candidate for the treatment of melanoma. For the in-vitro assay, murine B16-F10 melanoma cells were treated with 0.5, 1, 5, 10, 20 or 50 mM DCA for 3 days, analyzed with the crystal violet method. The in-vivo effect of DCA was evaluated in B16-F10 tumor-bearing C57BL/6 mice treated with different doses of DCA (0, 25, 75 or 150 mg/kg) by gavage for 10 days, followed by measurement of tumor volume. Upon necropsy, representative slices of lung, liver, kidney, spleen and intestine were collected, processed and submitted for histopathological examination. The DCA concentrations of 10, 20 and 50 mM reduced B16-F10 cell viability after 48 and 72 h of treatment, whereas 20 and 50 mM were effective after 24 h of treatment. A significant reduction in tumor growth was observed in B16-F10 melanoma bearing mice at all doses, with no change in body weight or histology. DCA attenuates the growth of B16-F10 melanoma in vitro and in vivo, without systemic toxic effects. Therefore, DCA is a candidate for drug repurposing against melanomas.
Use of oral dichloroacetate for palliation of leg pain arising from metastatic poorly differentiated carcinoma: a case report. [2021]Dichloroacetate sodium (DCA) is a nonproprietary drug currently used for treatment of inherited mitochondrial diseases. It was discovered in 2007 that DCA promotes human cancer cell death by a novel mechanism. Soon after this discovery, physicians began using DCA off-label for cancer treatment in a palliative setting. A case report is presented of a 71-year-old male with poorly differentiated carcinoma of unknown primary metastatic to the right leg and liver who achieved excellent palliation of leg pain by using oral DCA after failing conventional therapy.
Dichloroacetate modulates cytokines toward T helper 1 function via induction of the interleukin-12-interferon-γ pathway. [2021]Dichloroacetate (DCA) is one of the new, promising anticancer drugs. DCA restores normal mitochondrial function and enables cancer cells to undergo apoptosis. In addition, DCA was found to modulate certain signaling pathways involving some transcription factors. The latter encouraged us to study DCA immunomodulatory activity on cytokines and their association with increasing DCA cancer cell cytotoxicity.