Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of VAL-083 in Patients With MGMT Unmethylated, Bevacizumab-naive Recurrent Glioblastoma|
- Overall Survival [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- Progression-free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Median Progression-Free Survival [ Time Frame: From randomization until progression or death, whichever occurs first, assessed up to 9 months ] [ Designated as safety issue: No ]
- Median Overall Survival [ Time Frame: From randomization to death from any cause, assessed up to 9 months ] [ Designated as safety issue: No ]
- Overall Response Rate [ Time Frame: From randomization to achievement of either complete response (CR) or partial response (PR), assessed up to 9 months ] [ Designated as safety issue: No ]
- Duration of Response Rate [ Time Frame: From the first occurrence of a documented, objective response until the time of relapse or death from any cause, assessed up to 9 months ] [ Designated as safety issue: No ]
- Number of participants with treatment-related adverse events assessed using NCI CTCAE v.4 [ Time Frame: assessed up to 9 months ] [ Designated as safety issue: Yes ]
- Quality of Life [ Time Frame: assessed up to 9 months ] [ Designated as safety issue: No ]MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)
|Study Start Date:||June 2016|
|Estimated Primary Completion Date:||December 2019 (Final data collection date for primary outcome measure)|
The dosing regimen for patients will be VAL-083 (40 mg/m2) administered IV for 3 consecutive days at the beginning of every 21-day cycle. Patients will continue to receive VAL 083, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation. In patients who demonstrate response or stable disease and tolerate therapy, permission to continue treatment beyond 12 cycles will be considered, but will require consent of the Sponsor.
|Active Comparator: Lomustine||
The dosing regimen for patients will be lomustine (90 mg/m2, with an option to escalate to 110 mg/m2) orally on day 1 at the beginning of each 42-day treatment cycle. Patients will continue to receive lomustine for up to 6, 42-day treatment cycles or until they fulfill one of the criteria for study discontinuation.
Recurrent glioblastoma (GBM) is characterized by a dismal prognosis, with a median overall survival of 6-9 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 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 on the order of weeks to months.
Prognosis and response to therapy is 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 two-arm study will compare VAL-083 to lomustine, a standard of care chemotherapy drug for recurrent glioblastoma.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02717962
|Contact: Lorena Lopezfirstname.lastname@example.org|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Active, not recruiting|
|Houston, Texas, United States, 77030|