newly diagnosed and recurrent grade IV astrocytoma astrocytoma primary brain tumour
Conditions
Interventions
Patients should take their precribed doses of TMZ and BGB-290.
BGB-290:
Arm A, Arm B, and Arm C: 60 mg will be administered PO BID, once in the morning
and once in the evening 12 hours apart, conti
Sponsors
BeiGene USA, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: ALL PATIENTS 1) Age >=18 years old 2) Confirmed diagnosis of glioblastoma (WHO Grade IV). 3) Ability to undergo serial MRIs. 4) ECOG status = 14 days after a biopsy or >=28 days after an open biopsy or craniotomy with adequate wound healing. 10) Documented unmethylated MGMT promoter status.;Subjects in Arm C ESCALATION only must also meet inclusion criteria: 11) Documentation of MGMT promoter status • It is preferable to determine MGMT status by MS-PCR. Other acceptable platforms include pyrosequencing methodologies and MSHRM assays with comparable sensitivity, applied to archival or fresh tumor tissue. 12) No prior systemic chemotherapy other than TMZ for GB and nd no prior anti-angiogenic therapy 13) Histologically confirmed secondary glioblastoma 14) Progressive disease > 2 months after completion of first line therapy. 15) Disease that is evaluable or measurable by mRANO ;Subjects in Arm C EXPANSION only must also meet inclusion criteria: 16) Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy as defined by one or more of the following: • PD >= 3 months after the end of radiotherapy • PD that is clearly outside the radiation field • PD that has been unequivocally proven by surgery/biopsy 17) Disease that is measurable as defined by RANO criteria 18) Documentation of MGMT promoter status. For full list of inclusion criteria refer to the study protocol.
Exclusion criteria
Exclusion criteria: ALL PATIENTS 1) Chemotherapy, biologic therapy, immunotherapy or investigational agent =2, except for AEs not constituting a safety risk by investigator judgement 3) Major surgical procedure, open biopsy, or significant traumatic injury 2 years ago with no current evidence of disease and no therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b, all Arms • Incidence and nature of DLTs • Incidence, nature, and severity of AEs, graded according to the NCI-CTCAE, v4.03 • Number of cycles (Arm C Only) and the dose intensity of each component of the treatment regimens, and changes in vital signs and clinical laboratory test results during and following study treatment Phase 2, Arm A (BGB-290 + RT) and Arm B (BGB-290 + RT + TMZ) • Modified disease control rate (DCR) as assessed using the modified Response Assessment in Neuro-Oncology (mRANO), version 1.1 Phase 2, Arm C (BGB-290 + TMZ) • Objective response rate (ORR) as assessed using mRANO | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1b, all Arms: • PK parameter for pamiparib of steady-state Ctrough • Modified DCR (Arms A and B), DCR (Arm C), ORR and clinical benefit rate (CBR) • Time-to-event endpoints: e.g., duration of response (DOR), progression-free survival (PFS) and overall survival (OS) Phase 2, Arm A (BGB-290 + RT) and Arm B (BGB-290 + RT + TMZ): • ORR and CBR as assessed using RANO criteria • Time-to-event endpoints: e.g., DOR, PFS and OS Incidence, nature, and severity of AEs, graded according to NCI-CTCAE, v4.03 • The Dose intensity of each component of the treatment regimens, and changes in vital signs and clinical laboratory test results during and following study treatment • PK parameter for pamiparib Phase 2, Arm C (BGB-290 + TMZ): • DCR and CBR as assessed using RANO criteria • Time-to-event endpoints: e.g., DOR, PFS and OS • Incidence, nature, and severity of AEs, graded according to NCI-CTCAE, v4.03 • Number of cycles and the dose intensity of each component of the treatment regimens, and changes in vital signs and clinical laboratory test results during and following study treatment • PK parameter for pamiparub | — |
Countries
Netherlands
Outcome results
None listed