For Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma

For Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma

Trial Summary

Official Title

Phase II Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma

Status

Recruiting

Condition

Glioma, Glioblastoma, Glioblastoma Multiforme, GBM, Brain Cancer

Actual Start Date

January 20, 2017

Estimated Primary Completion Date

September 2020

About the Trial

Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma

We have initiated enrollment of a Phase 2 study of VAL-083 (dianhydrogalactitol) in patients with MGMT-unmethylated, Avastin (bevacizumab)-naïve recurrent glioblastoma.

This trial is being conducted in collaboration with the University of Texas MD Anderson Cancer Center.

To be eligible for the trial, patients must have histologically confirmed GBM with MGMT promoter-unmethylated, which has recurred following chemoradiation.

Enrolled patients will receive VAL-083 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. In patients who demonstrate response or stable disease and tolerate therapy, permission to continue treatment beyond 12 cycles will be considered.

Response to VAL-083 treatment will be assessed prior to each treatment cycle. The goal of this Phase 2 clinical trial is to determine if treatment with VAL-083 improves overall survival compared to historical control.

Detailed Info

Brief Summary

The purpose of this phase 2, single arm, biomarker-driven study is to determine if treatment of O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated recurrent glioblastoma with VAL-083 improves overall survival (OS), compared to historical control.

Study Phase

Phase 2

Estimated Enrollment

48

Estimated Primary Completion Date

September 2020

Study Type

Interventional

Interventions
  • Drug: VAL-083, Dianhydrogalactitol
Sponsor

DelMar Pharmaceuticals, Inc.

Eligibility

Gender

Male & Female

18+

Age

18 years and older

>60

Karnofsky Score

Higher than 60%

Inclusion Criteria

  1. Last dose of chemotherapy: At least 4 weeks
  2. 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.
  3. Patients must be ≥ 18 years old.
  4. Patients must have histologically confirmed initial diagnosis of primary intracranial World Health Organization (WHO) Grade IV malignant glioma (glioblastoma, GBM), now recurrent. Patients with recurrent disease whose initial diagnostic pathology confirmed glioblastoma will not need re-biopsy. Alternately, patients with prior intracranial low-grade glioma or anaplastic glioma will be eligible, if histologic assessment demonstrates transformation to GBM (first diagnosis of secondary GBM).
  5. Patients must have radiographic evidence of recurrent/progressive GBM after prior therapy (biopsy or resection and chemoradiation); 1st recurrence of GBM only, per Response Assessment in Neuro-Oncology Criteria (RANO) criteria. Histologically documented transformation from a lower grade gliomas will be considered first recurrence.
  6. Patients must have confirmed GBM MGMT status (tumor must be MGMT promoter unmethylated) by central laboratory Clinical Laboratory Improvement Amendments (CLIA) certified testing at MD Anderson, prior to registration. If initial MGMT testing obtained at an outside institution, MGMT status must be centrally retested at MD Anderson.
  7. Patients must have Karnofsky Performance Status (KPS) > 60%.
  8. Patients must have been previously treated for GBM with radiation with concurrent and adjuvant temozolomide chemotherapy.
  9. 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.
  10. Patients must ≥ 12 weeks from radiotherapy, to minimize the potential for magnetic resonance imaging (MRI) changes related to treatment (pseudo progression) that might be misdiagnosed as true progression of disease, unless the patient fulfills criteria for early progressive disease by RANO.
  11. 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.
  12. Patients must be at least 4 weeks from last dose of chemotherapy.
  13. Patients must be at least 4 weeks or 5 half-lives (whichever is shorter) from the last dose of prior investigational anti-cancer drugs.
  14. Patients must have recovered from all treatment-related toxicities to Grade 1 or less.
  15. If receiving corticosteroids, patients must be on a stable or decreasing dose of corticosteroids for ≥ 5 days prior to baseline MRI.
  16. Patients must have a predicted life expectancy of at least 12 weeks.
  17. Patients must have adequate bone marrow and organ function.
  18. Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests and accessible for follow-up.
  19. If the patient has been using the Optune™ device, it will be discontinued before initiating treatment with either study medication, and per inclusion criterion listed above, the patient must have recovered from all treatment-related toxicities to Grade 1 or less.
  20. Pregnancy restrictions - Women of childbearing potential must have a negative B-HCG documented within 7 days prior to registration

Exclusion Criteria

  1. Within 12 weeks of chemoradiation unless the patient fulfills criteria for early progressive disease by RANO
  2. Receipt of investigational agents within 5 half-lives of last dose of investigational agent
  3. Concurrent use of other investigational agents or Optune™ device
  4. Prior therapy with lomustine
  5. Prior therapy with bevacizumab
  6. 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 PI
  7. Evidence of leptomeningeal spread of disease
  8. Need for urgent palliative intervention (e.g., impending herniation)
  9. 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
  10. Use of medications known to be strong inhibitors of CYP3A4 up to 14 days before Cycle 1 Day 1
  11. Patients with a known sensitivity to any of the products to be administered during treatment
  12. Patients unable to undergo MRI of the brain
  13. 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.

Location

The following cities have clinical trial sites. Please check back often as locations will be updated.

Enrollment

For more information on enrollment into the current VAL-083 trial, please contact us or visit clinicaltrials.gov for location information.

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 is being done to determine if treatment of O-6-methylguanine-DNA methyltransferase (MGMT) unmethylated recurrent glioblastoma with VAL-083 improves overall survival (OS), compared to historical control.

This clinical trial has certain criteria that a person has to meet to determine if they can participate. After you have discussed the trial with your doctor, specific tests will be done to see if you qualify for this study.

DelMar Pharmaceuticals, Inc. is sponsoring this clinical trial.

The total number of patients enrolled in this clinical trial will be 48 subjects. These patients will receive VAL-083 at 40 mg/m2 IV on days 1, 2, and 3, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation (disease progression, death, intolerable toxicities, investigator's judgment, or withdrawal of consent). Disease status will be evaluated with clinical and MRI evaluation every other 21-day cycle, while the patient is receiving VAL-083 treatment, and then approximately every 42 ± 7 days while remaining on study. Symptom burden will be evaluated using the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) completed by patients at baseline and at the time of each imaging evaluation.

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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.