Safety Study of VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression

NCT03050736 | Completed Phase 2

• 1 other identifier: DLM-14-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase 2, open-label, single-arm study is to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in combination with a standard of care radiation regimen when used to treat newly diagnosed GBM in patients with unmethylated promoter of the methylguanine-DNA methyltransferase (uMGMT) gene. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated.

Conditions

Glioma; Glioblastoma; Glioblastoma Multiforme; GBM; Brain Cancer

Keywords

Glioma; Glioblastoma; Glioblastoma multiforme; GBM; brain tumor; brain cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy evaluation of tumor response in patients, as measured by magnetic resonance imaging

  Tumor response assessment via MRI, as long as patient continues to demonstrate response or stable disease and tolerates therapy.

  Every 42 days while receiving radiotherapy then every 63 days while remaining on study, from patient randomization until study discontinuation for up to 10 months

Secondary Outcomes (12)

• Safety evaluation of VAL-083 in combination with a standard radiation therapy, as determined by incidence of patient adverse events and changes in laboratory results, ECG and vital signs

  Every 30 days, from patient randomization through 28 days following last study treatment for up to 10 months

• Ctrough

  On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose

• Cmax

  On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose

• Tmax

  On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose

• AUClast

  On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose

Study Arms (1)

VAL-083 (Dianhydrogalactitol)

EXPERIMENTAL

VAL-083 given by intravenous infusion with a starting dose of 20 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts.

Drug: VAL-083 (Dianhydrogalactitol)

Interventions

VAL-083 (Dianhydrogalactitol) DRUG

VAL-083 given by intravenous infusion with a starting dose of 20 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts.

VAL-083 (Dianhydrogalactitol)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed histologically proven supratentorial GBM
• Tumor tissue specimens from the GBM surgery or open biopsy must be available for MGMT gene promoter status analysis and central pathology review.
• Documented unmethylated MGMT gene promoter status
• Males or females ≥18\< 70 years of age.
• Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
• Cranial MRI must have been performed within 21 days of study entry and MRI must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI performed within 72 hours of resection is preferred
• Stable or decreasing dose of steroids for ≥5 days prior to randomization.
• Karnofsky performance score ≥ 70%
• Patients must begin treatment with VAL-083 chemotherapy no sooner than 2 weeks and no later than 4 weeks from the diagnostic surgery.
• ANC ≥1,500/ µl
• Platelet count ≥ 100,000/µl
• Hemoglobin ≥ 10 gm/dl
• AST, ALT \< 2.5 times ULN
• Bilirubin \< 2.5 ULN
• Serum creatinine ≤ 1.5x ULN or creatinine clearance \> 50 mL/min (measured or calculated by the Cockcroft-Gault formula) (Cockcroft, 1976) at screening

You may not qualify if:

• Prior chemotherapy within the last 5 years.
• Prior radiation therapy of the head.
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of VAL-083.
• Prior systemic anti-angiogenic therapy.
• Placement of Gliadel® wafer at surgery.
• Planned surgery for other diseases (e.g. dental extraction).
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥5 years are eligible for this study.
• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Clinically manifest myocardial insufficiency (New York Heart Association \[NYHA\] III, IV) or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
• Inability to undergo Gd-MRI.
• Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• Subject is pregnant (positive serum beta human chorionic gonadotropin \[b-HCG\] test at screening) or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
• Current alcohol dependence or drug abuse.
• Known hypersensitivity to the study treatment.

Sponsors & Collaborators

• Kintara Therapeutics, Inc.: lead
• Sun Yat-sen University: collaborator

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, 510060, China

Location

Related Publications (1)

• Guo C, Yang Q, Deng M, Qiu X, Wu S, Du X, Sai K, Dai Z, Chen Z, Zhang J, Lin F, Ke C, Xi S, Hu W, Zhou Z, Li J, Cao X, Liao Y, Lv Y, Brown D, Langlands J, Johnson G, Bacha J, Kwan C, Kanekal S, Schwartz R, Chen Z. VAL-083 is effective in patients with newly-diagnosed MGMT-unmethylated glioblastoma: report of phase II study. Discov Oncol. 2025 Dec 12. doi: 10.1007/s12672-025-04235-y. Online ahead of print.

  PMID: 41385182 DERIVED

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

• Chen Zhong-ping, M.D., Ph.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: February 13, 2017
• Study Start: December 17, 2017
• Primary Completion: November 22, 2021
• Study Completion: December 30, 2024
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)