Oncology - Glioblastoma (GBM) MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: STIVARGA
Product Name: STIVARGA (Regorafenib)
Product Code: [na]
Pharmaceutical Form: Tablet
INN or Proposed INN: REGORAFENIB
CAS Number: 755037-03-7
Current Sponsor code: na
Concentration
Sponsors
Global Coalition for Adaptive Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Inclusion Criteria - Newly Diagnosed: • Age = 18 years. • Histologically confirmed Grade IV GBM/gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry [IHC] or sequencing for IDH) established following either a surgical resection or biopsy. • - An MRI scan performed within 21 days prior to randomization preferably. • Use of no more than 4mg of dexamethasone per day within 5 days prior to randomization. • Karnofsky performance status = 60% performed within a 14-day window prior to randomization. • Availability of tumor tissue representative of GBM from definitive surgery or biopsy. Main Inclusion Criteria - Recurrent: • Age = 18 years. • Histologically confirmed GBM/gliosarcoma (WHO criteria; non-IDH R132H mutant) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum Radiation Therapy (RT). • Evidence of recurrent disease (RD) demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria. • Use of no more than 4mg of dexamethasone per day within 5 days prior to randomization. • Baseline MRI performed within 14 days prior to randomization. • Karnofsky performance status = 70% performed within a 14-day window prior to randomization. • Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 277 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 78
Exclusion criteria
Exclusion criteria: Main Exclusion Criteria - Newly Diagnosed: • Any prior treatment for glioma including: prior prolifeprospan 20 with carmustine wafer; prior intracerebral agent; prior radiation treatment for GBM or lower-grade glioma; prior chemotherapy or immunotherapy for GBM or lower-grade glioma. • Receiving additional, concurrent, active therapy for GBM outside of the trial • Extensive leptomeningeal disease. • QTc > 450 msec if male and QTc > 470 msec if female. • History of another malignancy in the previous 3 years, with a disease-free interval of 450 msec if male and QTc > 470 msec if female. • History of another malignancy in the previous 3 years, with a diseasefree interval of < 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. • Laboratory results that meet exclusionary parameters. Main Exclusion Criteria - Recurrent Exclusion Criteria: • Early disease progression prior to 3 months (12 weeks) from the completion of RT. • More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of Temozolomide (TMZ) with an experimental agent is considered one line of chemotherapy.). • Any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other VEG)- or VEGF receptormediated targeted agent. • Any prior treatment with prolifeprospan 20 with carmustine wafer. • Any prior treatment with an intracerebral agent. • Receiving additional, concurrent, active therapy for GBM outside of the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To identify experimental therapies that improve overall survival (OS) for GBM patients in the Screening stage (Stage 1), determining if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment. • To confirm identified efficacious experimental therapies and associated biomarker signatures in an expansion stage (Stage 2) designed to support a new drug application. ;Secondary Objective: • To evaluate Progression Free Survival (PFS), duration of response, and tumour response by each biomarker/therapeutic combination. • To evaluate OS by each biomarker/therapeutic combination. • To determine short- and long-term safety signals and quality of life (QOL) measures of an experimental Arm in GBM patients versus standard of care. Exploratory Objectives: • To generate general prognostic and predictive biomarker hypotheses. • To build and validate a longitudinal endpoint model of OS comprised of early assessments (eg, performance status, disease progression) that are associated with OS. ;Primary end point(s): Overall Survival: defined from the time of randomization to death from any cause.;Timepoint(s) of evaluation of this end point: Overall Survival: defined from the time of randomization to death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression-Free Survival: defined as the time from randomization to clinically determined progression or death from any cause. •Tumor Response:complete response, partial response, progressive disease, stable disease. • Duration of Response:(Complete Response + Partial Response) defined as time from date of response to date of clinically determined disease progression or death from any cause.;Timepoint(s) of evaluation of this end point: • Progression-Free Survival: defined as the time from randomization to clinically determined progression or death from any cause. • Tumor Response:complete response, partial response, progressive disease, stable disease. • Duration of Response:(Complete Response + Partial Response) defined as time from date of response to date of clinically determined disease progression or death from any cause. | — |
Countries
Australia, Austria, Canada, China, France, Germany, Italy, Switzerland, United States
Contacts
Public ContactSenior Clinical Project Manager
IQVIA Biotech
Outcome results
None listed