Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Glioblastoma in the Adjuvant or Recurrent Setting

NCT02717962 | Completed Phase 2 FDA Drug

• 1 other identifier: DLM-16-001
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioma; Glioblastoma; Glioblastoma Multiforme; GBM; Brain Cancer

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; temozolomide failure; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Length of time from start of treatment (Day 1) until patient death

  Every 30 days from randomization until patient death

Secondary Outcomes (8)

• Estimate Progression-free Survival

  Every 30 days from randomization until disease progression or patient death, whichever occurs earlier

• Estimate Median Progression-Free Survival

  Every 30 days from randomization until disease progression or patient death, whichever occurs earlier

• Estimate Median Overall Survival

  Every 30 days from randomization until patient death

• Estimate Overall Response Rate

  Every 42 days from randomization to achievement of either complete response (CR) or partial response (PR)

• Estimate Duration of Response

  Every 42 days from the first occurrence of a documented, objective response until the time of relapse or patient death

Study Arms (2)

VAL-083, Dianhydrogalactitol (Group 1)

EXPERIMENTAL

Patients with recurrent/progressive GBM

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

Drug: VAL-083, Dianhydrogalactitol

Interventions

VAL-083, Dianhydrogalactitol DRUG

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.

VAL-083, Dianhydrogalactitol (Group 1); VAL-083, Dianhydrogalactitol (Group 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must willingly provide written consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
• Patients must be ≥ 18 years old.
• Patients must have histologically confirmed initial diagnosis of primary intracranial WHO Grade IV malignant glioma (glioblastoma).
• Patients must have preliminary GBM MGMT status (tumor must be MGMT promoter unmethylated) determined prior to study entry. If initial MGMT status is determined to be "unmethylated", by an outside institution the patient may be enrolled and begin treatment. However, MGMT status must be retested following enrollment by central laboratory CLIA certified testing at MD Anderson.
• Patients must have Karnofsky Performance Status (KPS) \> 60% (i.e., 70, 80, 90 or 100).
• Adequate recovery from all recent surgery is required. At least 21-days must have elapsed from the time of any major surgery, including craniotomy/tumor resection. Patients must have recovered from all surgery-related toxicities to Grade 1 or less.
• Prior therapy with gamma knife or other focal high-dose radiation is allowed, but at least 2 weeks must have elapsed from the time of treatment, and the patient must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field.
• Patients having prior therapy with Laser Induced Thermal Therapy (LITT) is allowed, but at least 21 days must have elapsed from last LITT, with recovery from all LITT-related toxicities to Grade 1 or less and subsequent histologic documentation of recurrence
• Patients must be at least 4 weeks from last dose of chemotherapy.
• Patients must have recovered from all treatment-related toxicities to Grade 1 or less.
• If receiving corticosteroids, patients must be on a stable or decreasing dose of corticosteroids for ≥ 5 days prior to baseline MRI.
• Patients must have a predicted life expectancy of at least 12 weeks.
• Patients must have adequate bone marrow and organ function.
• Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and accessible for follow-up after treatment termination.
• Pregnancy restrictions - Women of childbearing potential must have a negative B-HCG documented within 7 days prior to registration

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Kintara Therapeutics, Inc.: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Brain Neoplasms

Interventions

Dianhydrogalactitol

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Galactitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Barbara O'Brien, M.D.

  University of Texas, MDAnderson Cancer Center, Houston, Texas, USA 77030

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 24, 2016
• Study Start: January 20, 2017
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)