GliomaPhase 1/2NCT01478178
Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma
A Phase 1/2 study testing VAL-083 (Dianhydrogalactitol) in people with Glioma and Glioblastoma, run by Kintara Therapeutics, Inc. at 5 sites in United States.
Trial summary
The purpose of this Phase 1/2, open-label, single-arm study is to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in patients with recurrent malignant glioma. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Glioma, Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- VAL-083 (Dianhydrogalactitol)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2011to Oct 2016
- Phase
- Phase 1/2
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be greater than or equal to 18 years old.
- Histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (glioblastoma), now recurrent; or Cohorts 2 and 3 only: progressive secondary brain tumor, has failed standard brain radiotherapy, and has brain tumor progression after at least one line of systemic therapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
- If GBM, previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both bevacizumab (Avastin) and temozolomide (Temodar), unless either or both are contraindicated.
- If GBM, greater than or equal to 12 weeks from radiotherapy, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field.
- Cohorts 2 \& 3 only: Patients with secondary brain tumors must be greater than or equal to 4 weeks from radiotherapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
- At least 4 weeks from last chemotherapy or bevacizumab (Avastin) therapy (6 weeks for nitrosourea or mitomycin C), or for chemotherapy regimes given continuously or on a weekly basis with limited potential for delayed toxicity, at least 2 weeks from last dose.
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- At least 21 days or 5 half-lives (whichever is shorter) since prior investigational anti-cancer drugs. A minimum of 10 days between termination of the investigational drug and administration of DAG is required
- Recovered from all treatment-related toxicities to Grade 1 or less.
- Must have a Karnofsky performance status of > 50 with a predicted life expectancy of at least 12 weeks.
- Must have known MGMT methylation and IDH1 mutation status to be screened for study entry.
Who cannot join
- Current history of neoplasm other than the entry diagnosis. Patients with previous cancers treated and cured with local therapy alone may be considered with approval of the Medical Monitor.
- Evidence of leptomeningeal spread of disease.
- Evidence of recent hemorrhage on baseline MRI of the brain.
- Concurrent severe, intercurrent illness.
- History of severe cardiac disease.
- Significant vascular disease.
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- History of stroke or transient ischemic attack within 6 months prior to beginning treatment.
- Concomitant medications that are known inducers of CYP.
- Concomitant medications that are strong inhibitors of cytochrome P450 and CYP3A up to 14 days before Cycle 1 Day 1 (pimozide, diltiazem, erythromycin, clarithromycin, and quinidine, and amiodarone up to 90 days before)
- Known to be HIV positive or to have an AIDS-related illness.
- Pregnant or breast feeding.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Sarah Cannon Research Institute
Denver, Colorado, 80218
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Mayo Clinic
Rochester, Minnesota, 55905
University of California, San Francisco, Division of Neuro-Oncology
San Francisco, California, 94143
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
Official title: Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma
The purpose of this Phase 1/2, open-label, single-arm study is to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in patients with recurrent malignant glioma. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated.
Read the detailed description
Recurrent glial tumors of the brain continue to be one of the most challenging malignancies to treat. Median survival for patients with recurrent disease is approximately 6 months for glioblastoma multiforme. Bevacizumab is used for treatment of recurrent disease; however patients who fail bevacizumab do not have many treatment options.
Metastases to the brain are the most common intracranial tumors in adults and occur ten times more frequently than primary brain tumors. It is estimated that 8 - 10% of cancer patients may develop symptomatic metastatic tumors in the brain. Systemic therapy is rarely used for primary treatment of brain metastases because many tumors that metastasize to the brain are not chemosensitive or have been already heavily pretreated with potentially effective agents, and poor penetration through the blood brain barrier is an additional concern.
Dianhydrogalactitol (DAG) rapidly penetrates both the cerebrospinal fluid (CSF) and the blood-brain barrier and accumulates in brain tissue. Clinical study of DAG in patients with GBM or with progressive secondary brain tumors is warranted. Patients with secondary brain metastases were allowed to enroll into the current protocol in Cohorts 2 and 3; however, enrollment ceased with Amendment 5 and will not be continued beyond Cohort 3.
This study will utilize a standard 3 + 3 dose escalation design, until the MTD or the maximum specified dose has been reached. In Phase 2, additional patients with GBM will be treated at the MTD (or other selected optimum Phase 2 dose) to measure tumor responses to treatment.
- Conditions
- Glioma, Glioblastoma, Glioblastoma Multiforme, GBM, Brain Cancer
- Being tested
- VAL-083 (Dianhydrogalactitol)
- Keywords
- Glioma, Glioblastoma, Glioblastoma multiforme, GBM, brain tumor, brain cancer, recurrent brain tumor, recurrent brain cancer, refractory brain tumor, refractory brain cancer, recurrent GBM, refractory GBM, recurrent glioma, refractory glioma, recurrent glioblastoma, refractory glioblastoma, recurrent glioblastoma multiforme, refractory glioblastoma multiforme, failed temodar, failed temozolomide
- Medical subject headings
- Glioma, Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VAL-083 (Dianhydrogalactitol)Drug
VAL-083 given by intravenous infusion with a starting dose of 1.5 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts.
| Study group | Role | What they receive |
|---|---|---|
| VAL-083 (Dianhydrogalactitol) | Experimental | VAL-083 given by intravenous infusion with a starting dose of 1.5 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts. Receives: Drug: VAL-083 (Dianhydrogalactitol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of maximum tolerated dose (MTD)
The determination of MTD will be based on analysis of tolerance data from the first cycle of therapy in each dose group.
Measured: Study Day 35
Secondary outcomes (2)
Evaluate tumor response in patients with recurrent malignant glioma
Tumor assessment every other treatment cycle, as long as patient continues to demonstrate response or stable disease and tolerates therapy.
Measured: Every 60 days
Characterization of Cycle 1 plasma pharmacokinetics
Plasma will be analyzed to estimate appropriate PK parameters (Cmax, Tmax, AUC, elimination half-life, drug clearance, mean residence time, and volume of distribution).
Measured: Cycle 1: 0, 0.25, 0.5, 1, 2, 4, 6 hrs and immediately prior to Cycle 1, Day 2 dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startOct 2011
- Primary completionDec 2015
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kintara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Howard A Burris, M.D., Principal investigator, Sarah Cannon Research Institute; Nashville, Tennessee 37203, USAManish Patel, M.D., Principal investigator, Florida Cancer Specialists, Sarasota, Florida 34232, USANicholas Butowski, M.D., Principal investigator, University of California, San Francisco, 94143, USASani Kizilbash, M.D., Principal investigator, Mayo Clinic, Rochester, Minnesota 55905, USAGerald Falchook, M.D., Principal investigator, Sarah Cannon Research Institute; Denver, Colorado 80218 USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478178
- Sponsor's protocol ID
- DLM-10-001
- Status last verified
- Aug 2025
- First submitted
- 14 Nov 2011
- Last updated
- 29 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: The Clinical Study Report for this trial will be prepared and provided to U.S. F.D.A. as required by applicable regulatory requirement(s). Each participating trial investigator has been provided a copy their patient data captured in the electronic data base for this trial.
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT01478178
- Acronym / sponsor ID
- DLM-10-001
- Conditions
- Glioma, Glioblastoma, Glioblastoma Multiforme, GBM, Brain Cancer
- Keywords
- Glioma, Glioblastoma, Glioblastoma multiforme, GBM, brain tumor, brain cancer, recurrent brain tumor, recurrent brain cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Kintara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 23 Nov 2011 (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.
The purpose of this Phase 1/2, open-label, single-arm study is to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in patients with recurrent malignant glioma. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated.
Detailed description
Recurrent glial tumors of the brain continue to be one of the most challenging malignancies to treat. Median survival for patients with recurrent disease is approximately 6 months for glioblastoma multiforme. Bevacizumab is used for treatment of recurrent disease; however patients who fail bevacizumab do not have many treatment options.
Metastases to the brain are the most common intracranial tumors in adults and occur ten times more frequently than primary brain tumors. It is estimated that 8 - 10% of cancer patients may develop symptomatic metastatic tumors in the brain. Systemic therapy is rarely used for primary treatment of brain metastases because many tumors that metastasize to the brain are not chemosensitive or have been already heavily pretreated with potentially effective agents, and poor penetration through the blood brain barrier is an additional concern.
Dianhydrogalactitol (DAG) rapidly penetrates both the cerebrospinal fluid (CSF) and the blood-brain barrier and accumulates in brain tissue. Clinical study of DAG in patients with GBM or with progressive secondary brain tumors is warranted. Patients with secondary brain metastases were allowed to enroll into the current protocol in Cohorts 2 and 3; however, enrollment ceased with Amendment 5 and will not be continued beyond Cohort 3.
This study will utilize a standard 3 + 3 dose escalation design, until the MTD or the maximum specified dose has been reached. In Phase 2, additional patients with GBM will be treated at the MTD (or other selected optimum Phase 2 dose) to measure tumor responses to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VAL-083 (Dianhydrogalactitol) | Experimental | Drug: VAL-083 (Dianhydrogalactitol)VAL-083 given by intravenous infusion with a starting dose of 1.5 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must be greater than or equal to 18 years old.
- Histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (glioblastoma), now recurrent; or Cohorts 2 and 3 only: progressive secondary brain tumor, has failed standard brain radiotherapy, and has brain tumor progression after at least one line of systemic therapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
- If GBM, previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both bevacizumab (Avastin) and temozolomide (Temodar), unless either or both are contraindicated.
- If GBM, greater than or equal to 12 weeks from radiotherapy, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field.
- Cohorts 2 \& 3 only: Patients with secondary brain tumors must be greater than or equal to 4 weeks from radiotherapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
Key exclusion criteria (11 listed)
- Current history of neoplasm other than the entry diagnosis. Patients with previous cancers treated and cured with local therapy alone may be considered with approval of the Medical Monitor.
- Evidence of leptomeningeal spread of disease.
- Evidence of recent hemorrhage on baseline MRI of the brain.
- Concurrent severe, intercurrent illness.
- History of severe cardiac disease.
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 |
|---|---|---|
| VAL-083 (Dianhydrogalactitol)VAL-083 given by intravenous infusion with a starting dose of 1.5 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts. | Drug | VAL-083 (Dianhydrogalactitol) |
Primary outcome
Determination of maximum tolerated dose (MTD)
Time frame: Study Day 35
The determination of MTD will be based on analysis of tolerance data from the first cycle of therapy in each dose group.
2 secondary outcomes
Evaluate tumor response in patients with recurrent malignant glioma
Time frame: Every 60 days
Characterization of Cycle 1 plasma pharmacokinetics
Time frame: Cycle 1: 0, 0.25, 0.5, 1, 2, 4, 6 hrs and immediately prior to Cycle 1, Day 2 dosing
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 29 Aug 2025.
- Individual participant dataSharing planned: No. The Clinical Study Report for this trial will be prepared and provided to U.S. F.D.A. as required by applicable regulatory requirement(s). Each participating trial investigator has been provided a copy their patient data captured in the electronic data base for this trial.
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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.
Howard A Burris, M.D. principal investigator
Sarah Cannon Research Institute; Nashville, Tennessee 37203, USA
Manish Patel, M.D. principal investigator
Florida Cancer Specialists, Sarasota, Florida 34232, USA
Nicholas Butowski, M.D. principal investigator
University of California, San Francisco, 94143, USA
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing VAL-083 (Dianhydrogalactitol) in people with Glioma and Glioblastoma, run by Kintara Therapeutics, Inc. at 5 sites in United States.
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 10 inclusion and 11 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 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Determination of maximum tolerated dose (MTD) (time frame: Study Day 35). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Aug 2025.