BGB-290-104: A Phase 1b/2 study to assess the safety, tolerability and efficacy of BGB-290 in combination with radiation therapy and/or temozolomide in subjects with first-line or recurrent/refractory glioblastoma
- Conditions
- newly diagnosed and recurrent grade IV astrocytomaastrocytomaprimary brain tumour
- Registration Number
- NL-OMON48745
- Lead Sponsor
- BeiGene USA, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
ALL PATIENTS
1) Age >=18 years old
2) Confirmed diagnosis of glioblastoma (WHO Grade IV).
3) Ability to undergo serial MRIs.
4) ECOG status <= 1.
5) Adequate bone marrow function.
6) Adequate renal and hepatic function.
7) Ability to swallow whole capsules. ;Subjects in Arms A and B (not Arm C) must also meet inclusion criteria:
8) No previous treatment for GB except surgery.
9) Able to start radiation therapy <= 49 days after surgery but >= 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.
ALL PATIENTS
1) Chemotherapy, biologic therapy, immunotherapy or investigational agent <=21 days (or <=5 half-lives, whichever is shorter) prior to Day 1
2) Unresolved acute effects of any prior therapy of Grade >=2, except for AEs not constituting a safety risk by investigator judgement
3) Major surgical procedure, open biopsy, or significant traumatic injury <=28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
• Placement of vascular access device is not considered major surgery.
4) Other diagnosis of malignancy
• Except for surgically excised non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, localized prostate cancer treated with curative intent, adequately treated low-stage bladder cancer, ductal carcinoma in situ treated surgically with curative intent, or a malignancy diagnosed >2 years ago with no current evidence of disease and no therapy <=2 years prior to Day 1
5) Active infection requiring systemic treatment
6) Active cardiac disease, inflammatory gastrointestinal disease, bleeding disorder (for details see protocol)
7) Anticoagulation with heparin, warfarin, or other anticoagulants (for details see protocol)8) Use <=10 days (or <=5 half-lives, whichever is shorter) prior to Day 1 or anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers including known enzyme inducing anti-epileptic drugs;For subjects in Arms B and C (NOT applicable to Arm A)
9) Known hypersensitivity to any temozolomide component or to dacarbazine (DTIC)
10) Have hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
For full list of exclusion criteria see protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase 1b, all Arms<br /><br>• Incidence and nature of DLTs<br /><br>• Incidence, nature, and severity of AEs, graded according to the NCI-CTCAE,<br /><br>v4.03<br /><br>• Number of cycles (Arm C Only) and the dose intensity of each component of the<br /><br>treatment regimens, and changes in vital signs and clinical laboratory test<br /><br>results during and following study treatment<br /><br><br /><br>Phase 2, Arm A (BGB-290 + RT) and Arm B (BGB-290 + RT + TMZ)<br /><br>• Modified disease control rate (DCR) as assessed using the modified Response<br /><br>Assessment in Neuro-Oncology (mRANO), version 1.1<br /><br><br /><br>Phase 2, Arm C (BGB-290 + TMZ)<br /><br>• Objective response rate (ORR) as assessed using mRANO</p><br>
- Secondary Outcome Measures
Name Time Method