GliomaPhase 2NCT02717962
Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Glioblastoma in the Adjuvant or Recurrent Setting
A Phase 2 study testing VAL-083, Dianhydrogalactitol in people with Glioma and Glioblastoma, run by Kintara Therapeutics, Inc. at 1 site in United States.
Trial summary
The purpose of this phase 2, two arm, biomarker-driven study is to determine if treatment of O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated glioblastoma with VAL-083 improves overall survival (OS), compared to historical control, in the adjuvant or recurrent setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- 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
- 118 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2017to 30 Dec 2024
- 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
None listed.
Who cannot join
- Within 12 weeks of chemoradiation unless the patient fulfills criteria for early progressive disease by RANO, for Group 1; and, more than 6 weeks from chemoradiation for Group 2.
- Receipt of investigational agents within 5 half-lives of last dose of investigational agent.
- Concurrent use of other investigational agents or Optune™ device
- Prior therapy with lomustine.
- Prior therapy with bevacizumab.
- 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 Sponsor.
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- Evidence of leptomeningeal spread of disease.
- Need for urgent palliative intervention (e.g., impending herniation).
- Severe, intercurrent illness including, but not limited to unstable systemic disease, including ongoing or active infection, uncontrolled hypertension, serious cardiac arrhythmia requiring medication, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with a known sensitivity to any of the products to be administered during treatment.
- Patients unable to undergo MRI of the brain.
- Women who are pregnant or lactating. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase 2 Study of VAL-083 Treatment for MGMT Unmethylated Bevacizumab-naïve Glioblastoma in the Adjuvant or Recurrent Setting
The purpose of this phase 2, two arm, biomarker-driven study is to determine if treatment of O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated glioblastoma with VAL-083 improves overall survival (OS), compared to historical control, in the adjuvant or recurrent setting.
Read the detailed description
Recurrent GBM is characterized by a dismal prognosis, with a median overall survival of 6.9 months. While a standard of care is established for the initial treatment of GBM - radiation with concurrent and adjuvant temozolomide chemotherapy - management of recurrent disease (NCCN, 2014) remains suboptimal. Treatment options include repeat surgery, re-irradiation, or chemotherapy (including experimental targeted therapies, biologic agents, and immunotherapies). Only a minority of patients has response to these treatments, and the resultant benefits in progression-free and overall survival are in the order of weeks to months.
Prognosis and response to therapy are known to be better in patients with a methylated MGMT promoter gene. Epigenetic silencing of MGMT by promoter methylation is an important factor in predicting outcome for patients with GBM treated with temozolomide. Approximately 66% of GBM tumors are MGMT unmethylated (high expression of MGMT), which through a MGMT repair mechanism, confers resistance to temozolomide, the standard chemotherapy treatment of GBM.
VAL-083, Dianhydrogalactitol (DAG), unlike temozolomide, is demonstrated to be active independent of MGMT resistance mechanisms, in vitro. Thus, it may provide a treatment option for those patients that are considered likely to be poor responders to temozolomide.
This is a non-comparative, two arm, biomarker-driven study with VAL-083 in GBM patients with either recurrent disease (Group 1) or newly diagnosed GBM patients requiring maintenance therapy after chemoradiation with temozolomide (Group 2).
Group 1: A total of up to 83 patients with recurrent/progressive GBM will be enrolled. This will include 35 patients treated at 40 mg/m2 and up to 48 patients treated at 30 mg/m2.
Group 2: Up to an additional 36 newly diagnosed GBM patients who have completed chemoradiation treatment with temozolomide and received no subsequent maintenance temozolomide will be enrolled.
Eligible patients will receive VAL-083 IV on days 1, 2, and 3, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation (disease progression, death, intolerable toxicities, investigator's judgment, or withdrawal of consent). Disease status will be evaluated with clinical and MRI evaluation every other 21-day cycle, while the patient is receiving VAL-083 treatment, and then approximately every 42 ± 7 days while remaining on study. Symptom burden will be evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) completed by patients at baseline and at the time of each imaging evaluation.
Interval medical histories, targeted physical exams, neurologic evaluations, complete blood counts, and other laboratory and safety assessments will be performed approximately every 21-days. Blood samples will be taken at Cycle 1 Day 1 pre-dose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion with VAL-083 to determine the PK profile and dose-exposure relationship of VAL-083.
Toxicity will be evaluated and documented using the NCI CTCAE version 4.
This study will take approximately 36 months to enroll.
- 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 bevacizumab, temodar failure
- 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, DianhydrogalactitolDrug
The dosing regimen for patients will be VAL-083 (30 mg/m2) administered IV for 3 consecutive days at the beginning of every 21-day cycle. Patients will continue to receive VAL 083, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| VAL-083, Dianhydrogalactitol (Group 1) | Experimental | Patients with recurrent/progressive GBM Receives: Drug: VAL-083, Dianhydrogalactitol |
| VAL-083, Dianhydrogalactitol (Group 2) | Experimental | Newly diagnosed GBM patients who have completed chemoradiation treatment with temozolomide and received no subsequent maintenance temozolomide Receives: Drug: VAL-083, Dianhydrogalactitol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Length of time from start of treatment (Day 1) until patient death
Measured: Every 30 days from randomization until patient death
Secondary outcomes (8)
Estimate Progression-free Survival
Time from start of treatment (Day 1) until to the first occurrence of progression or patient death, whichever occurs first
Measured: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier
Estimate Median Progression-Free Survival
The median length of time from start of treatment (Day 1) until to the first occurrence of progression or patient death, whichever occurs first
Measured: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier
Estimate Median Overall Survival
The median length of time from start of treatment (Day 1) until patient death
Measured: Every 30 days from randomization until patient death
Estimate Overall Response Rate
Overall number of tumor complete response (CR) or partial response (PR) determined via MRI assessment
Measured: Every 42 days from randomization to achievement of either complete response (CR) or partial response (PR)
Estimate Duration of Response
Length of time tumor continues to demonstrate either complete response (CR) or partial response (PR) via MRI assessment
Measured: Every 42 days from the first occurrence of a documented, objective response until the time of relapse or patient death
Safety evaluation of VAL-083 in patients
To confirm safety and tolerability of VAL-083 using NCI CTCAE v.4 to assess adverse events
Measured: From randomization up to 28 days following last study treatment
Patient Quality of Life Assessment
MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)
Measured: Every 42 days from randomization until disease progression
Plasma Pharmacokinetics
PK profile and dose-exposure relationship of VAL-083
Measured: Cycle 1 Day 1 predose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion of VAL-083
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study start20 Jan 2017
- Primary completion30 Dec 2024
- Study completion30 Dec 2024
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kintara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Barbara O'Brien, M.D., Principal investigator, University of Texas, MDAnderson Cancer Center, Houston, Texas, USA 77030
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02717962
- Sponsor's protocol ID
- DLM-16-001
- Status last verified
- Aug 2025
- First submitted
- 16 Mar 2016
- Last updated
- 29 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- 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 will be provided a copy their patient data captured in the electronic data base for this trial.
- Expanded access
- Available
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
- Phase 2 Study of VAL-083 Treatment for MGMT Unmethylated Bevacizumab-naïve Glioblastoma in the Adjuvant or Recurrent Setting
- ClinicalTrials.gov ID
- NCT02717962
- Acronym / sponsor ID
- DLM-16-001
- 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 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Kintara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Jan 2017 (actual)
- Primary completion
- 30 Dec 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 24 Mar 2016 (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 2, two arm, biomarker-driven study is to determine if treatment of O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated glioblastoma with VAL-083 improves overall survival (OS), compared to historical control, in the adjuvant or recurrent setting.
Detailed description
Recurrent GBM is characterized by a dismal prognosis, with a median overall survival of 6.9 months. While a standard of care is established for the initial treatment of GBM - radiation with concurrent and adjuvant temozolomide chemotherapy - management of recurrent disease (NCCN, 2014) remains suboptimal. Treatment options include repeat surgery, re-irradiation, or chemotherapy (including experimental targeted therapies, biologic agents, and immunotherapies). Only a minority of patients has response to these treatments, and the resultant benefits in progression-free and overall survival are in the order of weeks to months.
Prognosis and response to therapy are known to be better in patients with a methylated MGMT promoter gene. Epigenetic silencing of MGMT by promoter methylation is an important factor in predicting outcome for patients with GBM treated with temozolomide. Approximately 66% of GBM tumors are MGMT unmethylated (high expression of MGMT), which through a MGMT repair mechanism, confers resistance to temozolomide, the standard chemotherapy treatment of GBM.
VAL-083, Dianhydrogalactitol (DAG), unlike temozolomide, is demonstrated to be active independent of MGMT resistance mechanisms, in vitro. Thus, it may provide a treatment option for those patients that are considered likely to be poor responders to temozolomide.
This is a non-comparative, two arm, biomarker-driven study with VAL-083 in GBM patients with either recurrent disease (Group 1) or newly diagnosed GBM patients requiring maintenance therapy after chemoradiation with temozolomide (Group 2).
Group 1: A total of up to 83 patients with recurrent/progressive GBM will be enrolled. This will include 35 patients treated at 40 mg/m2 and up to 48 patients treated at 30 mg/m2.
Group 2: Up to an additional 36 newly diagnosed GBM patients who have completed chemoradiation treatment with temozolomide and received no subsequent maintenance temozolomide will be enrolled.
Eligible patients will receive VAL-083 IV on days 1, 2, and 3, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation (disease progression, death, intolerable toxicities, investigator's judgment, or withdrawal of consent). Disease status will be evaluated with clinical and MRI evaluation every other 21-day cycle, while the patient is receiving VAL-083 treatment, and then approximately every 42 ± 7 days while remaining on study. Symptom burden will be evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) completed by patients at baseline and at the time of each imaging evaluation.
Interval medical histories, targeted physical exams, neurologic evaluations, complete blood counts, and other laboratory and safety assessments will be performed approximately every 21-days. Blood samples will be taken at Cycle 1 Day 1 pre-dose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion with VAL-083 to determine the PK profile and dose-exposure relationship of VAL-083.
Toxicity will be evaluated and documented using the NCI CTCAE version 4.
This study will take approximately 36 months to enroll.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VAL-083, Dianhydrogalactitol (Group 1) | Experimental | Drug: VAL-083, DianhydrogalactitolPatients with recurrent/progressive GBM |
| VAL-083, Dianhydrogalactitol (Group 2) | Experimental | Drug: VAL-083, DianhydrogalactitolNewly diagnosed GBM patients who have completed chemoradiation treatment with temozolomide and received no subsequent maintenance temozolomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (12 listed)
- Within 12 weeks of chemoradiation unless the patient fulfills criteria for early progressive disease by RANO, for Group 1; and, more than 6 weeks from chemoradiation for Group 2.
- Receipt of investigational agents within 5 half-lives of last dose of investigational agent.
- Concurrent use of other investigational agents or Optune™ device
- Prior therapy with lomustine.
- Prior therapy with bevacizumab.
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, DianhydrogalactitolThe dosing regimen for patients will be VAL-083 (30 mg/m2) administered IV for 3 consecutive days at the beginning of every 21-day cycle. Patients will continue to receive VAL 083, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation. | Drug | VAL-083, Dianhydrogalactitol (Group 1), VAL-083, Dianhydrogalactitol (Group 2) |
Primary outcome
Overall Survival
Time frame: Every 30 days from randomization until patient death
Length of time from start of treatment (Day 1) until patient death
8 secondary outcomes
Estimate Progression-free Survival
Time frame: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier
Estimate Median Progression-Free Survival
Time frame: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier
Estimate Median Overall Survival
Time frame: Every 30 days from randomization until patient death
Estimate Overall Response Rate
Time frame: Every 42 days from randomization to achievement of either complete response (CR) or partial response (PR)
Estimate Duration of Response
Time frame: Every 42 days from the first occurrence of a documented, objective response until the time of relapse or patient death
Safety evaluation of VAL-083 in patients
Time frame: From randomization up to 28 days following last study treatment
Patient Quality of Life Assessment
Time frame: Every 42 days from randomization until disease progression
Plasma Pharmacokinetics
Time frame: Cycle 1 Day 1 predose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion of VAL-083
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 will be 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.
Barbara O'Brien, M.D. principal investigator
University of Texas, MDAnderson Cancer Center, Houston, Texas, USA 77030
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 VAL-083, Dianhydrogalactitol in people with Glioma and Glioblastoma, run by Kintara Therapeutics, Inc. at 1 site 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 0 inclusion and 12 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 1 site 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 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?
Overall Survival (time frame: Every 30 days from randomization until patient death). 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.