For Patients With Recurrent Malignant Glioma

For Patients With Recurrent Malignant Glioma

Trial Summary

Official Title

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

Status

Completed

Condition

Glioma, Glioblastoma, Glioblastoma Multiforme, GBM, Brain Cancer

Actual Start Date

October 2011

Estimated Primary Completion Date

December 2015

About the Trial

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

We have completed a Phase 1/2 open-label, single arm dose- escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-cancer activity of VAL-083 in patients with GBM who have failed both bevacizumab (Avastin™) and temozolomide (Temodar™), unless either or both were contra-indicated.

Data from the trial were presented at the 2016 Annual Meeting of the Society for Clinical Oncology (ASCO). These data demonstrate that a dosing regimen of 40mg/m2/day VAL-083 on days 1-3 of a 21-day cycle was well tolerated in patients with bevacizumab-failed GBM.

Median survival of patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following Avastin™ (bevacizumab) failure compared to published literature where survival of approximately two to five months has been reported.

2016 ASCO Presentation

Detailed Info

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.

Study Phase

Phase 1/Phase 2

Estimated Enrollment

55

Estimated Primary Completion Date

December 2015

Study Type

Interventional

Interventions
  • Drug: VAL-083 (Dianhydrogalactitol)
Sponsor

DelMar Pharmaceuticals, Inc.

Eligibility

Gender

Male & Female

18+

Age

18 years and older

>50

Karnofsky Score

Higher than 50%

Inclusion Criteria

  1. Last dose of chemotherapy: At least 4 weeks
  2. Patients must be greater than or equal to 18 years old.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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
  9. Recovered from all treatment-related toxicities to Grade 1 or less.
  10. Must have a Karnofsky performance status of > 50 with a predicted life expectancy of at least 12 weeks.
  11. Must have known MGMT methylation and IDH1 mutation status to be screened for study entry.

Exclusion Criteria

  1. 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.
  2. Evidence of leptomeningeal spread of disease.
  3. Evidence of recent hemorrhage on baseline MRI of the brain.
  4. Concurrent severe, intercurrent illness.
  5. History of severe cardiac disease.
  6. Significant vascular disease.
  7. History of stroke or transient ischemic attack within 6 months prior to beginning treatment.
  8. Concomitant medications that are known inducers of CYP.
  9. 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)
  10. Known to be HIV positive or to have an AIDS-related illness.
  11. Pregnant or breast feeding.

Location

The following cities had VAL-083 clinical trial sites.

Enrollment

This study has been completed.

Frequently Asked Questions

A Clinical Trial is a type of research study that examines how well a potential therapy works in humans.

This clinical trial was done 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.

DelMar Pharmaceuticals, Inc. is sponsoring this clinical trial.

The total number of patients enrolled in this clinical trial will be 55 subjects. This trial utilized a standard 3 + 3 dose escalation design, until the MTD or the maximum specified dose was been reached. In Phase 2, additional patients with GBM were treated at the MTD (or other selected optimum Phase 2 dose) to measure tumor responses to treatment.

This study has been completed.

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.

The safety and efficacy of the investigational use of this product has not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.