Ignite Creation Date:
2024-05-06 @ 8:20 AM
Last Modification Date:
2024-10-26 @ 11:59 AM
Study NCT ID:
NCT02717962
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-22
First Post:
2016-03-16
Brief Title:
Study of VAL-083 in Patients With MGMT Unmethylated Bevacizumab-naive Glioblastoma in the Adjuvant or Recurrent Setting
Sponsor:
Kintara Therapeutics Inc
Organization:
Kintara Therapeutics Inc
Study Overview
Official Title:
Phase 2 Study of VAL-083 Treatment for MGMT Unmethylated Bevacizumab-naïve Glioblastoma in the Adjuvant or Recurrent Setting
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
True
If Expanded Access, NCT#:
NCT03138629
Has Expanded Access, NCT# Status:
NO_LONGER_AVAILABLE
Acronym:
None
Brief Summary:
The purpose of this phase 2 two arm biomarker-driven study is to determine if treatment of O-6-methylguanine-DNA methyltransferase MGMT unmethylated glioblastoma with VAL-083 improves overall survival OS compared to historical control in the adjuvant or recurrent setting
Detailed Description:
Recurrent GBM is characterized by a dismal prognosis with a median overall survival of 69 months While a standard of care is established for the initial treatment of GBM - radiation with concurrent and adjuvant temozolomide chemotherapy - management of recurrent disease NCCN 2014 remains suboptimal Treatment options include repeat surgery re-irradiation or chemotherapy including experimental targeted therapies biologic agents and immunotherapies Only a minority of patients has response to these treatments and the resultant benefits in progression-free and overall survival are in the order of weeks to months
Prognosis and response to therapy are known to be better in patients with a methylated MGMT promoter gene Epigenetic silencing of MGMT by promoter methylation is an important factor in predicting outcome for patients with GBM treated with temozolomide Approximately 66 of GBM tumors are MGMT unmethylated high expression of MGMT which through a MGMT repair mechanism confers resistance to temozolomide the standard chemotherapy treatment of GBM
VAL-083 Dianhydrogalactitol DAG unlike temozolomide is demonstrated to be active independent of MGMT resistance mechanisms in vitro Thus it may provide a treatment option for those patients that are considered likely to be poor responders to temozolomide
This is a non-comparative two arm biomarker-driven study with VAL-083 in GBM patients with either recurrent disease Group 1 or newly diagnosed GBM patients requiring maintenance therapy after chemoradiation with temozolomide Group 2
Group 1 A total of up to 83 patients with recurrentprogressive GBM will be enrolled This will include 35 patients treated at 40 mgm2 and up to 48 patients treated at 30 mgm2
Group 2 Up to an additional 36 newly diagnosed GBM patients who have completed chemoradiation treatment with temozolomide and received no subsequent maintenance temozolomide will be enrolled
Eligible patients will receive VAL-083 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 investigators 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
Interval medical histories targeted physical exams neurologic evaluations complete blood counts and other laboratory and safety assessments will be performed approximately every 21-days Blood samples will be taken at Cycle 1 Day 1 pre-dose 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 with VAL-083 to determine the PK profile and dose-exposure relationship of VAL-083
Toxicity will be evaluated and documented using the NCI CTCAE version 4
This study will take approximately 36 months to enroll
Prognosis and response to therapy are known to be better in patients with a methylated MGMT promoter gene Epigenetic silencing of MGMT by promoter methylation is an important factor in predicting outcome for patients with GBM treated with temozolomide Approximately 66 of GBM tumors are MGMT unmethylated high expression of MGMT which through a MGMT repair mechanism confers resistance to temozolomide the standard chemotherapy treatment of GBM
VAL-083 Dianhydrogalactitol DAG unlike temozolomide is demonstrated to be active independent of MGMT resistance mechanisms in vitro Thus it may provide a treatment option for those patients that are considered likely to be poor responders to temozolomide
This is a non-comparative two arm biomarker-driven study with VAL-083 in GBM patients with either recurrent disease Group 1 or newly diagnosed GBM patients requiring maintenance therapy after chemoradiation with temozolomide Group 2
Group 1 A total of up to 83 patients with recurrentprogressive GBM will be enrolled This will include 35 patients treated at 40 mgm2 and up to 48 patients treated at 30 mgm2
Group 2 Up to an additional 36 newly diagnosed GBM patients who have completed chemoradiation treatment with temozolomide and received no subsequent maintenance temozolomide will be enrolled
Eligible patients will receive VAL-083 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 investigators 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
Interval medical histories targeted physical exams neurologic evaluations complete blood counts and other laboratory and safety assessments will be performed approximately every 21-days Blood samples will be taken at Cycle 1 Day 1 pre-dose 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 with VAL-083 to determine the PK profile and dose-exposure relationship of VAL-083
Toxicity will be evaluated and documented using the NCI CTCAE version 4
This study will take approximately 36 months to enroll
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None