A Phase Ib/II Clinical Study of BBI608 in Combination With Temozolomide for Adult Patients With Recurrent or Progressed Glioblastoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 34
- Locations
- 3
- Primary Endpoint
- Dose-limiting Toxicities (DLTs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm A
Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.
Intervention: BBI608 (Drug)
Arm A
Patients for whom surgery is recommended as part of treatment for recurrent Glioblastoma.
Intervention: Temozolomide (Drug)
Arm B
Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.
Intervention: BBI608 (Drug)
Arm B
Patients for whom surgery is not recommended as part of the treatment for recurrent Glioblastoma.
Intervention: Temozolomide (Drug)
Outcomes
Primary Outcomes
Dose-limiting Toxicities (DLTs)
Time Frame: 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
Time Frame: 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 Outcomes
- Disease Control Rate (DCR)(4 weeks)
- 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)
- Overall Response Rate (ORR)(4 weeks)
- 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)
- 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)
- 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.)