Malignant Gliomas, Glioblastoma MultiformePhase 2NCT00540176
The Safety and Efficacy of DCA for the Treatment of Brain Cancer
A Phase 2 study testing Dichloroacetate (DCA) in people with Malignant Gliomas, Glioblastoma Multiforme, run by University of Alberta at 1 site in Canada.
Trial summary
Malignant gliomas, which include Glioblastoma multiforme (GBM), are the most common and most aggressive types of brain cancer, accounting for approximately 60% of primary brain tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Gliomas, Glioblastoma Multiforme
- What is being tested?
- Dichloroacetate (DCA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2007to Aug 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed intracranial malignant glioma / GBM tumors.
- All patients enrolled must have measurable with or without evaluable disease, as defined in Section 11.
- In the recurrent malignant glioma cohort of patients, four weeks must have elapsed from prior chemotherapy or radiation therapy.
- Age 18 years and over.
- ECOG (Eastern Cooperative Oncology Group) performance status Grade 0-2 (Karnofsky >70).
- Life expectancy of greater than 12 weeks.
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- Patients must have liver, kidney and marrow function as defined below:
- absolute neutrophil count >1,500/mcL
- hemoglobin >90 g/L
- platelets >100,000/mcL
- total bilirubin <1.5 X upper limit of normal (ULN)
- AST(SGOT) and ALT(SGPT) <1.5 X ULN
- creatinine <1.5 X ULN
- Recovery to baseline or, at most, grade 1 of all drug-related toxicities due to prior chemotherapy, radiation, or molecular targeted therapy, except for alopecia.
- Women of child-bearing potential and men must agree to use adequate contraception (e.g.: hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Patients must be able to understand and be willing to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy, molecular targeted therapy, or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients with new onset or increasing dose regimen of steroids for the week prior to enrollment.
- Patients cannot be receiving any other investigational therapies.
- Patients with grade 2 or higher peripheral neuropathy due to prior medical condition (such as multiple sclerosis, diabetes etc), medications (chemotherapy), or other etiologies.
- Greater than 0.8 cm brain midline shift on CT scan or MRI
- Any psychological, familial, sociological, or geographical conditions that do not permit medical follow-up and compliance with the study protocol.
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- Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes with history of significant hypoglycemic episodes in the past 3 months or psychiatric illness/social situations that would limit compliance with study requirements.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with DCA. In addition, these patients are at increased risk of lethal (and at time intracranial) infections when treated with potentially marrow-suppressive therapy.
- History of malabsorption syndrome or substantial amount of small bowels or stomach resection or obstruction that may impair absorption of DCA.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Open-labeled, Double-arm Clinical Study of Dichloroacetate (DCA) in Malignant Gliomas and Glioblastome Multiforme (GBM) Patients
Malignant gliomas, which include Glioblastoma multiforme (GBM), are the most common and most aggressive types of brain cancer, accounting for approximately 60% of primary brain tumors. These tumors are characterized by diverse molecular abnormalities (within the same tumor), which, along with the difficulties of many standard chemotherapies crossing the blood barrier, contribute to the very poor response to therapy and poor survival.
We recently showed that Dichloroacetate (DCA, an inhibitor of the mitochondrial pyruvate dehydrogenase kinase) was able to depolarize cancer (but not normal) mitochondria and induce apoptosis in cancer but not normal tissues. We believe that altering the metabolism of cancers like glioblastoma (DCA switches metabolism from the cytoplasmic glycolysis to the mitochondrial glucose oxidation) we inhibit the resistance to apoptosis that characterizes cancer. Because metabolism (i.e. glycolysis) is the end result of many and diverse molecular pathways, the effects of DCA might be positive in cancers with diverse molecular backgrounds. DCA is also a very small molecule that readily crosses the blood brain barrier. Therefore we hypothesize that DCA will be an effective and relative non-toxic potential therapy for malignant gliomas.
Read more
We are conducting a phase II trial with 2 parallel arms: a) patients with newly diagnosed malignant gliomas and b) patients with recurrent gliomas or gliomas that have failed standard therapy (which includes surgery, radiotherapy and chemotherapy). All patients need to have a histological diagnosis. DCA will be given orally and patients will be followed for a minimum of 6 months. The tumor size will be followed by standard MRI or CT criteria and glucose uptake (a direct effect of DCA on the tumor) will be measured by FDG-PET imaging. Several clinical parameters and quality of life will be followed. Potential toxicity (particularly peripheral neuropathy) will be closely followed and dose-de-escalation protocols are in place in case of toxicity. In addition, escape protocols for the application of standard therapy (when appropriate) are in place in patients with no evidence of response to DCA. In vitro studies will be performed in the tissues obtained at the time of surgery (where appropriate) and correlated prospectively with clinical data.
There is limited ability to accept patients outside of Alberta; this is in part because the visit and testing schedule is intense, requiring residence in Edmonton for at least 6 months.
- Being tested
- Dichloroacetate (DCA)
- Keywords
- Dichloroacetate, Glioblastoma Multiforme, Glioma
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dichloroacetate (DCA)Drug
Oral DCA given twice daily for the 24 week period of the study. Continuation of therapy will be indefinite if efficacious.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Recurrent disease with previous surgery, radiation therapy and/or chemotherapy Receives: Drug: Dichloroacetate (DCA) |
| Cohort B | Experimental | Newly diagnosed disease with no previous therapy Receives: Drug: Dichloroacetate (DCA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the therapeutic response to oral Dichloroacetate (DCA) in patients with malignant gliomas, utilizing standard criteria for the objective response of tumor size to treatment (CT and/or MRI).
To evaluate the safety and tolerability of oral (DCA) in patients with gliomas.
To determine the progression-free survival (PFS) and overall survival achieved with oral DCA in patients with gliomas.
Secondary outcomes (2)
• To evaluate the in vitro effects of DCA on cell proliferation/apoptosis and mitochondrial function in malignant glioma tissues taken from enrolled patients at the time of surgery and correlate them with clinical data.
• To evaluate glucose uptake using 18F-FDG Positron Emission Tomography (PET) scanning as a biological marker for predicting subsequent therapeutic response to oral DCA in patients with malignant gliomas.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant Gliomas, Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Capital Health, Canada
- Responsible party
- Sponsor
- Investigators
- Kenneth Petruk, MD co-PI, Principal investigator, University of Alberta and Capital HealthEvangelos D Michelakis, MD co-PI, Principal investigator, University of Alberta and Capital HealthConnor Maguire MD, investigator, Principal investigator, University of Alberta and Capital HealthLinda Webster, NP manager, Study director, Capital Health, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00540176
- Sponsor's protocol ID
- DCA 10002
- Status last verified
- Feb 2010
- First submitted
- 4 Oct 2007
- Last updated
- 13 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007 Jan;11(1):37-51. doi: 10.1016/j.ccr.2006.10.020.
PubMed 17222789
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-labeled, Double-arm Clinical Study of Dichloroacetate (DCA) in Malignant Gliomas and Glioblastome Multiforme (GBM) Patients
- ClinicalTrials.gov ID
- NCT00540176
- Acronym / sponsor ID
- DCA 10002
- Keywords
- Dichloroacetate, Glioblastoma Multiforme, Glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Capital Health, Canada
- Study start
- Oct 2007
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 5 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Malignant gliomas, which include Glioblastoma multiforme (GBM), are the most common and most aggressive types of brain cancer, accounting for approximately 60% of primary brain tumors. These tumors are characterized by diverse molecular abnormalities (within the same tumor), which, along with the difficulties of many standard chemotherapies crossing the blood barrier, contribute to the very poor response to therapy and poor survival.
We recently showed that Dichloroacetate (DCA, an inhibitor of the mitochondrial pyruvate dehydrogenase kinase) was able to depolarize cancer (but not normal) mitochondria and induce apoptosis in cancer but not normal tissues. We believe that altering the metabolism of cancers like glioblastoma (DCA switches metabolism from the cytoplasmic glycolysis to the mitochondrial glucose oxidation) we inhibit the resistance to apoptosis that characterizes cancer. Because metabolism (i.e. glycolysis) is the end result of many and diverse molecular pathways, the effects of DCA might be positive in cancers with diverse molecular backgrounds. DCA is also a very small molecule that readily crosses the blood brain barrier. 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 parallel arms: a) patients with newly diagnosed malignant gliomas and b) patients with recurrent gliomas or gliomas that have failed standard therapy (which includes surgery, radiotherapy and chemotherapy). All patients need to have a histological diagnosis. DCA will be given orally and patients will be followed for a minimum of 6 months. The tumor size will be followed by standard MRI or CT criteria and glucose uptake (a direct effect of DCA on the tumor) will be measured by FDG-PET imaging. Several clinical parameters and quality of life will be followed. Potential toxicity (particularly peripheral neuropathy) will be closely followed and dose-de-escalation protocols are in place in case of toxicity. In addition, escape protocols for the application of standard therapy (when appropriate) are in place in patients with no evidence of response to DCA. In vitro studies will be performed in the tissues obtained at the time of surgery (where appropriate) and correlated prospectively with clinical data.
There is limited ability to accept patients outside of Alberta; this is in part because the visit and testing schedule is intense, requiring residence in Edmonton for at least 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: Dichloroacetate (DCA)Recurrent disease with previous surgery, radiation therapy and/or chemotherapy |
| Cohort B | Experimental | Drug: Dichloroacetate (DCA)Newly diagnosed disease with no previous therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have histologically confirmed intracranial malignant glioma / GBM tumors.
- All patients enrolled must have measurable with or without evaluable disease, as defined in Section 11.
- In the recurrent malignant glioma cohort of patients, four weeks must have elapsed from prior chemotherapy or radiation therapy.
- Age 18 years and over.
- ECOG (Eastern Cooperative Oncology Group) performance status Grade 0-2 (Karnofsky >70).
Key exclusion criteria (9 listed)
- Patients who have had chemotherapy, molecular targeted therapy, or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients with new onset or increasing dose regimen of steroids for the week prior to enrollment.
- Patients cannot be receiving any other investigational therapies.
- Patients with grade 2 or higher peripheral neuropathy due to prior medical condition (such as multiple sclerosis, diabetes etc), medications (chemotherapy), or other etiologies.
- Greater than 0.8 cm brain midline shift on CT scan or MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dichloroacetate (DCA)Oral DCA given twice daily for the 24 week period of the study. Continuation of therapy will be indefinite if efficacious. | Drug | Cohort A, Cohort B |
Primary outcome
To determine the therapeutic response to oral Dichloroacetate (DCA) in patients with malignant gliomas, utilizing standard criteria for the objective response of tumor size to treatment (CT and/or MRI).
To evaluate the safety and tolerability of oral (DCA) in patients with gliomas.
To determine the progression-free survival (PFS) and overall survival achieved with oral DCA in patients with gliomas.
2 secondary outcomes
• To evaluate the in vitro effects of DCA on cell proliferation/apoptosis and mitochondrial function in malignant glioma tissues taken from enrolled patients at the time of surgery and correlate them with clinical data.
• To evaluate glucose uptake using 18F-FDG Positron Emission Tomography (PET) scanning as a biological marker for predicting subsequent therapeutic response to oral DCA in patients with malignant gliomas.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2014.
- Background: PubMed 17222789Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007 Jan;11(1):37-51. doi: 10.1016/j.ccr.2006.10.020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Petruk, MD co-PI principal investigator
University of Alberta and Capital Health
Evangelos D Michelakis, MD co-PI principal investigator
University of Alberta and Capital Health
Connor Maguire MD, investigator principal investigator
University of Alberta and Capital Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dichloroacetate (DCA) in people with Malignant Gliomas, Glioblastoma Multiforme, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the therapeutic response to oral Dichloroacetate (DCA) in patients with malignant gliomas, utilizing standard criteria for the objective response of tumor size to treatment (CT and/or MRI).. The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00540176, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2014.