Summary

for people ages 18-99 (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Nicholas Butowski

Description

Summary

This study is to evaluate the safety, efficacy and clinical activity of BGB-290 in combination with radiation therapy (RT) and/or temozolomide (TMZ) in subjects with newly diagnosed or recurrent/refractory glioblastoma.

Official Title

A Phase 1b/2 Study to Assess the Safety, Tolerability and Efficacy of BGB-290 in Combination With Radiation Therapy (RT) and/or Temozolomide (TMZ) in Subjects With First-line or Recurrent/Refractory Glioblastoma

Details

An open‑label, multiple‑dose, dose-escalation study to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BGB-290 in combination with radiation therapy (RT) and/or TMZ with 2 arms and a potential third arm.

In dose escalation/Phase 1b, BGB-290 will be combined with RT (Arm A) or RT and TMZ (Arm B) in subjects with newly diagnosed unmethylated glioblastoma (GB), or BGB-290 will be combined with TMZ in subjects with methylated or unmethylated recurrent/refractory GB (Arm C).

The dose expansion/Phase 2 phase will enroll up to 4 cohorts: subjects with newly diagnosed unmethylated GB in Arm A and Arm B, and 2 potential cohorts of subjects with unmethylated and methylated recurrent/refractory GB in Arm C. Subjects in dose expansion may continue treatment in the absence of safety concerns and disease progression.

Keywords

Brain and Central Nervous System Tumors Adult glioblastoma, adult gian cell glioblastoma, adult gliosarcoma, glioma neoplasms recurrent adult brain tumor neoplasms, central nervous system neoplasms, neoplasms by histologic type, neoplasms by site astrocytoma neuroepithelial neuroectodermal tumors germ cell and embryonal antineoplastic agents glandular and epithelial nerve tissue, nervous system diseases temozolomide BGB-290 alkylating, alkylating agents molecular mechanisms of pharmacological action Poly(ADP-ribose) polymerase inhibitors enzyme inhibitors Glioblastoma Nervous System Neoplasms Central Nervous System Neoplasms Dacarbazine TMZ Radiation

Eligibility

You can join if…

Open to people ages 18-99

All subjects

  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. Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 90 days after last dosing.
  8. Ability to swallow whole capsules.

Subjects in Arms A and B (not Arm C) must also meet inclusion criteria 9 - 10:

  1. No previous treatment for GB except surgery.
  2. . 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.
  3. . Documented unmethylated MGMT promoter status.

Subjects in Arm C must also meet inclusion criteria # 12 - 14:

  1. . No prior systemic chemotherapy other than TMZ for GB.
  2. . Progressive disease > 2 months after completion of first line therapy.
  3. . At least one measurable lesion by mRANO.

Subjects in Arm C Phase 2, Cohort C1 must also meet criteria # 15. This is not applicable to subjects enrolled in Arm C, Ph 1b.

  1. . Documentation of unmethylated MGMT promoter status.

Subjects in Arm C Phase 2, Cohort C2 must also meet Criteria #16. This is not applicable to subjects enrolled in Arm C Phase 1b.

  1. . Documentation of methylated MGMT promoter status.

You CAN'T join if...

All subjects

  1. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents ≤21 days prior to start of study treatment.
  2. Toxicity of ≥ Grade 2 from prior therapy.
  3. Major surgery or significant other injury ≤ 4 weeks prior to start of study treatment.
  4. History of other active malignancies within 2 years with exception of (i) adequately treated in situ cancer of the cervix, (ii) non-melanoma skin cancer, or (iii)localized adequately treated cancer with curative intent or malignancy diagnosed > 2 years ago with no evidence of disease and no treatment ≤ 2 years prior to study treatment.
  5. Uncontrolled seizure disorder.
  6. Active infection requiring systemic treatment.
  7. Known human immunodeficiency virus (HIV) or active viral hepatitis.
  8. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease,ventricular arrhythmia or CVA ≤ 6 months prior to start of treatment.
  9. Active clinically significant gastrointestinal disease.
  10. . Active bleeding disorder ≤ 6 months prior to start of treatment.
  11. . Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.
  12. . Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
  13. . Pregnant or nursing females.
  14. . Significant intercurrent illness that may result in subject's death prior to death from glioblastoma.
  15. . Known hypersensitivity to any component of TMZ or decarbazine (DTIC). [Subjects in Arms B and C only.]

Locations

  • University of California at San Francisco accepting new patients
    San Francisco California 94143 United States
  • UCLA Neuro-Oncology not yet accepting patients
    Los Angeles California 90095 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
BeiGene USA, Inc.
ID
NCT03150862
Phase
Phase 1/2
Lead Scientist
Nicholas Butowski
Study Type
Interventional
Last Updated