VAL-083 Phase 3 Study in Temozolomide-Avastin (Bevacizumab) Recurrent GBM
brief summary
This is an adaptive design, randomized controlled, Phase 3 clinical trial in patients with glioblastoma multiforme (GBM) or gliosarcoma (GS), previously treated with surgery (if appropriate), standard of care chemo-radiation with temozolomide, +/- adjuvant temozolomide, and bevacizumab and now has progressive disease during or after bevacizumab. A total of up to 180 eligible patients with recurrent/progressive GBM or GS will be randomized to receive either the investigational drug (VAL-083) or "Investigator's choice of salvage therapy" as a contemporaneous control, in a 2:1 fashion. Up to 120 eligible patients will be randomized to receive VAL-083 at 40 mg/m2 IV on days 1, 2, and 3 of a 21-day treatment-cycle, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation. Up to 60 patients will be randomized to receive "Investigator's choice of salvage therapy", limited to temozolomide, lomustine, or carboplatin, until they fulfill one of the criteria for study discontinuation. The dose level for Investigator's choice salvage therapy (temozolomide, lomustine, or carboplatin), will be in accordance with the product label or institutional guidelines. In both study arms, interval medical histories, targeted physical exams, neurologic evaluations, complete blood counts, and other laboratory and safety assessments will be performed approximately every 21-days while receiving treatment. Tumor assessments are to be performed approximately every 42 ± 7 days while remaining on study. The study is estimated to last approximately 20 months.
detailed description
This is an adaptive, randomized controlled, Phase 3 clinical trial in adult patients with histologically confirmed diagnosis of a recurrent glioblastoma multiforme (GBM) or gliosarcoma (GS), who have been previously treated with surgery (if appropriate), standard of care chemo-radiation with temozolomide, +/- adjuvant temozolomide, and bevacizumab and now have progressive disease during or after bevacizumab. Patients with prior low-grade glioma or anaplastic glioma are eligible, if histologic assessment demonstrates transformation to GBM or GS.
Treatment Groups: Eligible patients will be randomized to receive either the investigational drug (VAL-083) or "Investigator's choice of salvage therapy" as a contemporaneous control, in a 2:1 fashion. A total of up to 180 patients with recurrent/progressive GBM or GS will be enrolled; patients will be randomized to one of two treatment arms as follows:
Group 1: Up to 120 eligible patients will be randomized to receive VAL-083 at 40 mg/m2 IV on days 1, 2, and 3 of a 21-day treatment-cycle, for up to 12, 21-day treatment cycles or until they fulfill one of the criteria for study discontinuation (death, intolerable toxicities, investigator's judgment, or withdrawal of consent). In patients who demonstrate response, stable disease or who continue therapy at the discretion of the investigator following initial progression and tolerate therapy, permission to continue treatment beyond 12 cycles will be considered but will require consent of the Sponsor. VAL-083 will be administered as an IV infusion over 30-60 minutes.
Group 2: Up to 60 patients will be randomized to receive "Investigator's choice of salvage therapy" until they fulfill one of the criteria for study discontinuation (death, intolerable toxicities, investigator's judgment, or withdrawal of consent). "Investigator's choice of salvage therapy" will be limited to the following: temozolomide, lomustine, or carboplatin. The dose level for Investigator's choice salvage therapy (temozolomide, lomustine, or carboplatin), will be in accordance with the product label or institutional guidelines.
In both arms, disease status will be evaluated with clinical and imaging evaluation. Baseline total tumor burden must be assessed by MRI within 2 weeks prior to randomization. For patients randomized to VAL-083, post-baseline tumor assessments are to be performed prior to every other 21-day cycle for VAL-083, i.e., prior to Cycles 3, 5, etc., while the patient is receiving VAL-083 treatment, and then approximately every 42 ± 7 days while remaining on study. For patients randomized to the Physician's choice salvage therapy arm, post-baseline tumor assessments are to be performed approximately every 42 ± 7 days while remaining on study, as long as the patient continues to demonstrate response or stable disease or comes off the study.
official title
A Pivotal Randomized, Controlled Trial of VAL-083 in Patients With Recurrent Glioblastoma Who Have Failed Standard Temozolomide/Radiation Therapy and Bevacizumab (STAR-3)