Ignite Creation Date:
2024-05-06 @ 9:44 AM
Last Modification Date:
2024-10-26 @ 12:18 PM
Study NCT ID:
NCT03050736
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-11-21
First Post:
2017-01-27
Brief Title:
Safety Study of VAL-083 and Radiotherapy in Patients With Newly Diagnosed GBM Having Unmethylated MGMT Expression
Sponsor:
Kintara Therapeutics Inc
Organization:
Kintara Therapeutics Inc
Study Overview
Official Title:
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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
Malignant gliomas are the most common primary central nervous system tumors found in adults with WHO Grade IV malignant glioma GBM representing the most aggressive and prevalent sub-type of these tumors having one of the worst 5-year survival rates among all human cancers
Standard therapy for patients with malignant gliomas has traditionally involved maximal surgical resectiondebulking of the primary tumor if feasible followed by adjuvant radiotherapy over 6-8 weeks with or without chemotherapy The oral alkylating agent temozolomide was found to increase median survival when used in combination with radiotherapy compared to radiotherapy alone in patients with newly diagnosed GBM However expression of O6-methylguanine methyltransferase MGMT in GBM has been linked to poor patient outcome in patients treated with temozolomide
The study drug dianhydrogalactitol VAL 083 is a bi-functional N7 DNA alkylating agent which has demonstrated cytotoxic activity that is independent of chemo-resistance due to expression of MGMT This makes VAL-083 an ideal candidate to treat patients who are unlikely to respond to temozolomide due to MGMT expression in their GBM Furthermore VAL-083 acted as a radio-sensitizer at low 1 - 25μM concentrations in all GBM cultures tested
VAL-083 has been studied extensively in the United States by the National Cancer Institute The NCI studies suggested that VAL-083 appeared to have activity in some types of cancer lung and brain including GBM however further VAL-083 research was not pursued in the US due to an increased focus on targeted biologic therapies during that era VAL-083 has also been studied in the Peoples Republic of China where it is currently approved and marketed for treatment of chronic myeloid leukemia and lung cancer At present VAL-083 is being studied in clinical trials in the United States as a third-line treatment option for patients with recurrent GBM following failure of surgery radiation therapy temozolomide and bevacizumab Interim results support safety of VAL-083 in this population to date a regimen of 40mgm2d x 3 days IV in a 21 day cycle has been confirmed to be safe and well tolerated
This phase 2 open-label single arm study will be conducted in a dose-escalation cohort scheme to confirm the optimal dose of VAL-083 when administered concurrently with radiation therapy Dose escalation will proceed in three sequential cohorts consisting of patients receiving VAL-083 at 20 30 and 40 mgm2d x 3 every 21 days
This trial will be conducted in 2 parts Part 1 will consist of 1 a 42-day induction period during which patients will receive VAL-083 while undergoing radiation treatment at a dose of 2 Gy per fraction given once daily five days per week Monday through Friday over a period of six weeks for a total dose of 60 Gy followed by 2 adjuvant maintenance therapy with VAL-083 alone administered daily x 3 IV every 3 weeks at the same assigned dose for a maximum of 8 maintenance cycles Part 2 will comprise an expansion phase in which VAL-083 will be studied in up to 20 additional subjects The dose of VAL-083 that will be studied in Part 2 will be determined from Part 1
Patients will undergo safety assessments including physical examinations vital signs hematology serum chemistry and urinalysis
In both parts of the study a pharmacokinetic study may be conducted at treatment Cycle 1 Day 1 in consenting patients For patients consenting to CSF collection by lumbar puncture a CSF sample will be obtained after completion of the Cycle 1 Day 3 VAL-083 infusion These patients will also have a blood sample taken for VAL-083 plasma level after completion of drug infusion
Response parameters will be evaluated according to the Response Assessment in NeuroOncology RANO
Standard therapy for patients with malignant gliomas has traditionally involved maximal surgical resectiondebulking of the primary tumor if feasible followed by adjuvant radiotherapy over 6-8 weeks with or without chemotherapy The oral alkylating agent temozolomide was found to increase median survival when used in combination with radiotherapy compared to radiotherapy alone in patients with newly diagnosed GBM However expression of O6-methylguanine methyltransferase MGMT in GBM has been linked to poor patient outcome in patients treated with temozolomide
The study drug dianhydrogalactitol VAL 083 is a bi-functional N7 DNA alkylating agent which has demonstrated cytotoxic activity that is independent of chemo-resistance due to expression of MGMT This makes VAL-083 an ideal candidate to treat patients who are unlikely to respond to temozolomide due to MGMT expression in their GBM Furthermore VAL-083 acted as a radio-sensitizer at low 1 - 25μM concentrations in all GBM cultures tested
VAL-083 has been studied extensively in the United States by the National Cancer Institute The NCI studies suggested that VAL-083 appeared to have activity in some types of cancer lung and brain including GBM however further VAL-083 research was not pursued in the US due to an increased focus on targeted biologic therapies during that era VAL-083 has also been studied in the Peoples Republic of China where it is currently approved and marketed for treatment of chronic myeloid leukemia and lung cancer At present VAL-083 is being studied in clinical trials in the United States as a third-line treatment option for patients with recurrent GBM following failure of surgery radiation therapy temozolomide and bevacizumab Interim results support safety of VAL-083 in this population to date a regimen of 40mgm2d x 3 days IV in a 21 day cycle has been confirmed to be safe and well tolerated
This phase 2 open-label single arm study will be conducted in a dose-escalation cohort scheme to confirm the optimal dose of VAL-083 when administered concurrently with radiation therapy Dose escalation will proceed in three sequential cohorts consisting of patients receiving VAL-083 at 20 30 and 40 mgm2d x 3 every 21 days
This trial will be conducted in 2 parts Part 1 will consist of 1 a 42-day induction period during which patients will receive VAL-083 while undergoing radiation treatment at a dose of 2 Gy per fraction given once daily five days per week Monday through Friday over a period of six weeks for a total dose of 60 Gy followed by 2 adjuvant maintenance therapy with VAL-083 alone administered daily x 3 IV every 3 weeks at the same assigned dose for a maximum of 8 maintenance cycles Part 2 will comprise an expansion phase in which VAL-083 will be studied in up to 20 additional subjects The dose of VAL-083 that will be studied in Part 2 will be determined from Part 1
Patients will undergo safety assessments including physical examinations vital signs hematology serum chemistry and urinalysis
In both parts of the study a pharmacokinetic study may be conducted at treatment Cycle 1 Day 1 in consenting patients For patients consenting to CSF collection by lumbar puncture a CSF sample will be obtained after completion of the Cycle 1 Day 3 VAL-083 infusion These patients will also have a blood sample taken for VAL-083 plasma level after completion of drug infusion
Response parameters will be evaluated according to the Response Assessment in NeuroOncology RANO
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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