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

Launched by KINTARA THERAPEUTICS, INC. · Feb 8, 2017

Keywords

ClinConnect Summary

This clinical trial is studying the safety and effectiveness of a treatment called VAL-083 combined with standard radiation therapy for patients with newly diagnosed glioblastoma (GBM), a type of brain cancer. The trial specifically focuses on patients whose tumors have a certain genetic marker called unmethylated MGMT, which can affect how tumors respond to treatment. The goal is to find out the highest dose of VAL-083 that can be safely given to patients while monitoring how well the treatment works against the tumor.

To participate in this trial, patients must be between 18 and 70 years old and have a confirmed diagnosis of GBM. They should have had surgery or a biopsy to remove some of the tumor, and their tumor tissue needs to be tested for the unmethylated MGMT status. Participants will begin treatment with VAL-083 within a few weeks after their surgery and will undergo regular MRI scans to monitor their progress. It's important to note that certain health conditions and previous treatments may exclude a patient from joining the trial. Overall, this study aims to explore a new treatment approach and provide hope for better outcomes in GBM patients.

Gender

ALL

Eligibility criteria

• 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.