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Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma or Progressive Secondary Brain Tumor

Phase 1/Phase 2
18 Years
Open (Enrolling)
Glioma, Glioblastoma, Glioblastoma Multiforme, GBM, Brain Cancer

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Trial Information

Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma or Progressive Secondary Brain Tumor

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

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.

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 or
progressive secondary brain tumor will be treated at the MTD (or other selected optimum
Phase 2 dose) to measure tumor responses to treatment.

Inclusion Criteria:

- 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 progressive secondary brain tumor, has failed
standard brain radiotherapy, and has brain tumor progression after at least one line
of systemic therapy.

- 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.

- Patients with secondary brain tumors must be greater than or equal to 4 weeks from

- 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.

- Recovered from all treatment-related toxicities to Grade 1 or less.

- Must have a predicted life expectancy of at least 12 weeks.

Exclusion Criteria:

- 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.

- Prior treatment with prolifeprospan 20 with carmustine wafer (Gliadel wafer) within
60 days prior to first treatment (Day 0).

- Prior intracerebral agents.

- 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

- 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)

- Pregnant or breast feeding.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determination of maximum tolerated dose (MTD)

Outcome Description:

The determination of MTD will be based on analysis of tolerance data from the first cycle of therapy in each dose group.

Outcome Time Frame:

Study Day 35

Safety Issue:


Principal Investigator

Howard A Burris, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sarah Cannon Research Institute; Nashville, TN 37203, USA


United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

December 2013

Related Keywords:

  • Glioma
  • Glioblastoma
  • Glioblastoma Multiforme
  • GBM
  • Brain Cancer
  • 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 glioblastom 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
  • Brain Neoplasms
  • Glioblastoma
  • Glioma



Florida Cancer SpecialistsFort Myers, Florida  33901
Sarah Cannon Research InstituteNashville, Tennessee  37203