Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma

NCT01478178 | Completed Phase 1

• 1 other identifier: DLM-10-001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 5

Brief 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.

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 temodar; failed temozolomide; temodar refractory; temozolomide refractory; failed avastin; avastin refractory; failed bevacizumab; bevacizumab refractory; avastin failure; bevacizumab failure; temodar failure; temozolomide failure

Outcome Measures

Primary Outcomes (1)

• 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.

  Study Day 35

Secondary Outcomes (2)

• Evaluate tumor response in patients with recurrent malignant glioma

  Every 60 days

• Characterization of Cycle 1 plasma pharmacokinetics

  Cycle 1: 0, 0.25, 0.5, 1, 2, 4, 6 hrs and immediately prior to Cycle 1, Day 2 dosing

Study Arms (1)

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.

Drug: VAL-083 (Dianhydrogalactitol)

Interventions

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.

VAL-083 (Dianhydrogalactitol)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Kintara Therapeutics, Inc.: lead

Study Sites (5)

University of California, San Francisco, Division of Neuro-Oncology

San Francisco, California, 94143, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, 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

• Howard A Burris, M.D.

  Sarah Cannon Research Institute; Nashville, Tennessee 37203, USA

  PRINCIPAL INVESTIGATOR

• Manish Patel, M.D.

  Florida Cancer Specialists, Sarasota, Florida 34232, USA

  PRINCIPAL INVESTIGATOR

• Nicholas Butowski, M.D.

  University of California, San Francisco, 94143, USA

  PRINCIPAL INVESTIGATOR

• Sani Kizilbash, M.D.

  Mayo Clinic, Rochester, Minnesota 55905, USA

  PRINCIPAL INVESTIGATOR

• Gerald Falchook, M.D.

  Sarah Cannon Research Institute; Denver, Colorado 80218 USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 23, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: October 1, 2016
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)