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

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

About the Trial

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

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.

What is VAL-083?

VAL-083 represents a "first-in-class" small molecule chemotherapeutic, which means that the molecular structure of VAL-083 is not an analogue or derivative of other small molecule chemotherapeutics approved for the treatment of cancer.

Our Study

Condition

  • Glioma
  • Glioblastoma
  • Glioblastoma Multiforme
  • GBM
  • Brain Cancer

Study Type

Interventional

Study Design

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

Intervention Model

Single Group Assignment

Primary Purpose

Treatment

Masking

None (Open Label)

Primary Completion Date

September 2020

Outcomes

Primary Outcomes

  • Overall Survival
  • Every 30 days from randomization until patient death or for at least 9 months, whichever occurs earlier
  • Length of time from start of treatment (Day 1) until patient death

Secondary Outcomes

  • Estimate Progression-free Survival (Timeframe: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier, for at least 9 months)
  • Estimate Median Progression-Free Survival (Timeframe: Every 30 days from randomization until disease progression or patient death, whichever occurs earlier, for at least 9 months)
  • Estimate Median Overall Survival (Timeframe: Every 30 days from randomization until patient death or for at least 9 months, whichever occurs earlier)
  • Estimate Overall Response Rate (Timeframe: Every 42 days from randomization to achievement of either complete response (CR) or partial response (PR) for at least 9 months)
  • Estimate Duration of Response (Timeframe: Every 42 days from the first occurrence of a documented, objective response until the time of relapse or patient death, for at least 9 months, whichever occurs earlier)
  • Safety evaluation of VAL-083 in patients (Timeframe: From randomization up to 28 days following last study treatment)
  • Quality of Life (Timeframe: Every 42 days from randomization until disease progression, for at least 9 months)
  • Plasma Pharmacokinetics (Timeframe: Cycle 1 Day 1 predose, 15 ± 5 min, 30 ± 5 min, 60 ± 10 min, 120 ± 10 min, 240 ± 15 min, and 360 ± 15 min after the end of the of iv infusion of VAL-083)

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) 70 or higher.
  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. Patients with a known sensitivity to any of the products to be administered during treatment
  11. Patients unable to undergo MRI of the brain
  12. 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.

Requests for Expanded Access

This Policy for Requests for Expanded Access to Investigational Drugs describes the principles and procedures that DelMar Pharmaceuticals, Inc. will follow when considering requests by licensed physicians for use of DelMar’s investigational drugs outside of clinical trials.

View Policy

Enrollment

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

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.