A Study of BBI608 in Combination With Temozolomide in Adult Patients With Recurrent or Progressed Glioblastoma
- Registration Number
- NCT02315534
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This is an open label, multi-center, phase 1 safety run-in and phase 2 study of BBI608 in combination with temozolomide in patients with recurrent or progressive glioblastoma who have not received prior bevacizumab therapy.
- Detailed Description
In arm A, patients who are candidates for surgical resection will receive BBI608 as monotherapy prior to resection, followed by post-operative BBI608 administered in combination with temozolomide. In arm B, patients who are not candidates for surgical resection will receive BBI608 administered orally, daily, in combination with temozolomide.
In the phase 1/dose-limiting toxicity (DLT) cohort portion of this study, pharmacokinetics will be evaluated for both arms A and B. Pharmacodynamics will be evaluated in all patients who undergo surgical resection.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A BBI608 Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma. Arm B BBI608 Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma. Arm A Temozolomide Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma. Arm B Temozolomide Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.
- Primary Outcome Measures
Name Time Method Dose-limiting Toxicities (DLTs) 28 days after first administration of combination treatment (BBI608+TMZ) Number of patients who experienced a dose limiting toxicity following a dosing of BBI608
Progression Free Survival (PFS)-6 From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, assessed up to 6 months To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 6 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-6 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 6 months after treatment.
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) 4 weeks To assess the percentage of patients that had evaluable disease at baseline with a documented complete response, partial response, and stable disease (CR + PR + SD) based on the Response Assessment in Neuro-Oncology (RANO) criteria out of all patients who received at least one dose of any study drug and had evaluable disease at baseline.
Pharmacodynamic Activity of BBI608 When Administered in Combination With Temozolomide as Assessed by Tumor Biopsy and Cancer Stem Cell Assays as Well as the Concentration of Study Drug in Tumors At the time of surgical resection Tumor samples to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.
Overall Response Rate (ORR) 4 weeks The proportion of patients with a documented complete response and partial response (CR + PR) based on RANO criteria.
Pharmacokinetic Profile of BBI608 and Temozolomide When Administered in Combination With Temozolomide as Assessed by the Area Under the Curve On Day 1 and Day 5 after the first dosing, prior to dosing and 1, 2, 3, 5, 5h40m (day 1 only), 6, 7, 8 and 24 hours after first dose of BBI608 The area under the curve of BBI608, from time 0 to the last quantifiable concentration, calculated by a combination of linear and logarithmic trapezoidal methods (linear up/log down method)
Progression Free Survival (PFS)-12 From the time of exposure to study drug to first objective documentation of disease progression or death due to any cause, up to 12 months To assess the effect of BBI608 + temozolomide (TMZ) therapy defined as the percentage of patients who have survived without objective disease progression for at least 12 months after treatment per neuro-oncology (RANO) criteria who had evaluable disease at baseline. PFS-12 is defined as the percentage of patients who survived without objective disease progression per RANO criteria for at least 12 months after treatment.
Overall Survival (OS) From the time of exposure to study drug to death from any cause. If patient discontinued study drug, they were assessed the first 3 months after discontinuation, then every 3 months up to 1 year, then every 6 months thereafter until death. To assess the effect of BBI608 + temozolomide (TMZ) on the overall survival of patients with recurrent or progressive glioblastoma multiforme (GBM) who had not received prior treatment with bevacizumab or other anti-vascular endothelial growth factor agents who either were eligible or not eligible for surgical resection.
Trial Locations
- Locations (3)
Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada