Safety Study of VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression

Safety Study of VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression

About the Trial

An Open Label Trial of Dianhydrogalactitol (VAL-083) and Radiation Therapy in Treatment of Newly Diagnosed GBM Patients With An Unmethylated Promoter of the Methylguanine-DNA Methyltransferase (MGMT) Gene

The purpose of this Phase 2, open-label, single-arm study is to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in combination with a standard of care radiation regimen when used to treat newly diagnosed GBM in patients with unmethylated promoter of the methylguanine-DNA methyltransferase (uMGMT) gene. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated.

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

Safety Study of VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression Study Design

Intervention Model

Single Group Assignment

Primary Purpose

Treatment

Masking

No masking

Primary Completion Date

February 2019

Outcomes

Primary Outcomes

  • Efficacy evaluation of tumor response in patients, as measured by magnetic resonance imaging
  • Every 42 days while receiving radiotherapy then every 63 days while remaining on study, from patient randomization until study discontinuation for up to 10 months
  • Tumor response assessment via MRI, as long as patient continues to demonstrate response or stable disease and tolerates therapy.

Secondary Outcomes

  • Safety evaluation of VAL-083 in combination with a standard radiation therapy, as determined by incidence of patient adverse events and changes in laboratory results, ECG and vital signs (Timeframe: Every 30 days, from patient randomization through 28 days following last study treatment for up to 10 months)
  • Ctrough (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • Cmax (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • Tmax (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • AUClast (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • AUCinf (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • CL/F (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • Mean Residence Time (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • Vz (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • Lambda z (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • T½ (Timeframe: On Cycle 1 Day 1 pre-dose, and 15, 30, 60, 120, 240 and 360 minutes after study drug administration then Cycle 1 Day 2 pre-dose)
  • Pharmacokinetic profile and dose-exposure relationship of VAL-083 in Cerebral Spinal Fluid (CSF) (Timeframe: Once after completion of Cycle 1 Day 3 infusion)

Eligibility

Gender

Male & Female

18+

Age

18 years and older

≥70

Karnofsky Score

Equal or higher to 70

Inclusion Criteria

  1. Newly diagnosed histologically proven supratentorial GBM
  2. Tumor tissue specimens from the GBM surgery or open biopsy must be available for MGMT gene promoter status analysis and central pathology review.
  3. Documented unmethylated MGMT gene promoter status
  4. Males or females ≥18< 70 years of age.
  5. Interval of ≥2 weeks but ≤7 weeks after surgery or biopsy before first administration of study treatment.
  6. Cranial MRI must have been performed within 21 days of study entry and MRI must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI performed within 72 hours of resection is preferred
  7. Stable or decreasing dose of steroids for ≥5 days prior to randomization.
  8. Karnofsky performance score ≥ 70%
  9. Patients must begin treatment with VAL-083 chemotherapy no sooner than 2 weeks and no later than 4 weeks from the diagnostic surgery.
  10. ANC ≥1,500/ µl
  11. Platelet count ≥ 100,000/µl
  12. Hemoglobin ≥ 10 gm/dl
  13. AST, ALT < 2.5 times ULN
  14. Bilirubin < 2.5 ULN
  15. Serum creatinine ≤ 1.5x ULN or creatinine clearance > 50 mL/min (measured or calculated by the Cockcroft-Gault formula) (Cockcroft, 1976) at screening

Exclusion Criteria

  1. Prior chemotherapy within the last 5 years.
  2. Prior radiation therapy of the head.
  3. Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of VAL-083.
  4. Prior systemic anti-angiogenic therapy.
  5. Placement of Gliadel® wafer at surgery.
  6. Planned surgery for other diseases (e.g. dental extraction).
  7. History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
  8. History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥5 years are eligible for this study.
  9. History of coagulation disorder associated with bleeding or recurrent thrombotic events.
  10. Clinically manifest myocardial insufficiency (New York Heart Association [NYHA] III, IV) or history of myocardial infarction during the past 6 months; or uncontrolled arterial hypertension.
  11. Inability to undergo Gd-MRI.
  12. Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
  13. Subject is pregnant (positive serum beta human chorionic gonadotropin [b-HCG] test at screening) or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
  14. Current alcohol dependence or drug abuse.
  15. Known hypersensitivity to the study treatment.
  16. Legal incapacity or limited legal capacity.
  17. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  18. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

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.