Clinical Trial - NCT03150862

A Study Assessing BGB-290 With Radiation and/or Temozolomide (TMZ) in Subjects With Newly Diagnosed or Recurrent Glioblastoma

Recruiting

Sponsor: BeiGene USA, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03150862

Protocol Info

Short Description: Phase 1b/2 of BGB-290 + RT and/or Temozolomide in First-line or Recurrent/Refractory GBM
Long Description: 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
MGH Status: Open
Sponsor: BeiGene
Disease Program: Brain/CNS

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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.
Condition Title Intervention Phase
Brain and Central Nervous System Tumors BGB-290 TMZ Radiation Phase 1/Phase 2
Study Type Interventional
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

Primary Outcome Measures

Incidence and nature of dose limiting toxicities (DLTs) as assessed by CTCAE [Time Frame: From first dose BGB-290 to 10 weeks post-dose (Arms A and B). From first dose BGB-290 to 28 days post-dose (Arm C).] [Designated as safety issue: ]

Incidence, nature and severity of adverse events as assessed by CTCAE [Time Frame: From first dose BGB-290 to 30 days post-dose.] [Designated as safety issue: ]

Number of treatment cycles, dose intensity of components of each treatment regimen, and changes in vital signs and clinical laboratory tests during and following treatment [Time Frame: From first dose BGB-290 to 30 days post dose.] [Designated as safety issue: ]

Phase 2: Arm A [BGB-290 + RT] and Arm B [BGB-290 + RT + TMZ] [Time Frame: From first dose BGB-290 to first documentation of progression while subject is alive assessed up to 5 years.] [Designated as safety issue: ]

Phase 2 Arm C [BGB-290 + TMZ] [Time Frame: From first dose of BGB-290 to first documentation of progression assessed up to 5 years.] [Designated as safety issue: ]


Secondary Outcome Measures

Pharmacokinetic (PK) parameters of BGB-290 of steady state Ctrough [Time Frame: From first dose BGB-290 to 30 days post-dose.] [Designated as safety issue: ]

Modified disease control rate (DCR). (Arms A and B) [Time Frame: From first dose BGB-290 to first documentation of disease progression while subject is alive assessed up to 5 years] [Designated as safety issue: ]

Disease control rate (Arm C) [Time Frame: From first dose BGB-290 to first documentation of disease progression while subject is alive assessed up to 5 years] [Designated as safety issue: ]

Objective response rate (ORR) [Time Frame: From first dose BGB-290 to first documentation of disease progression assessed up to 5 years] [Designated as safety issue: ]

Clinical benefit rate (CBR). [Time Frame: From first dose BGB-290 to first documentation of disease progression assessed up to 5 years] [Designated as safety issue: ]

Duration of response (DOR). [Time Frame: From first dose BGB-290 to first documentation of disease progression assessed up to 5 years.] [Designated as safety issue: ]

Progression free survival (PFS). [Time Frame: From first dose BGB-290 until first documentation of disease progression or death, whichever is first, assessed up to 5 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: From first dose BGB-290 until date of death, assessed up to 5 years] [Designated as safety issue: ]

Objective response rate (ORR). [Time Frame: From the first dose BGB-290 to first documentation of disease progression, assessed up to 5 years] [Designated as safety issue: ]

Clinical benefit rate (CBR) [Time Frame: From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years] [Designated as safety issue: ]

Duration of response (DOR) [Time Frame: From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years] [Designated as safety issue: ]

Progression free survival (PFS) [Time Frame: From first dose BGB-290 until first documentation of disease progression or death, whichever is first, assessed up to 5 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: From first dose BGB-290 until date of death, assessed up to 5 years] [Designated as safety issue: ]

Incidence, nature and severity of adverse events as assessed by CTCAE [Time Frame: From first dose BGB-290 to 30 days post dose.] [Designated as safety issue: ]

Number of treatment cycles, dose intensity of components of each treatment regimen, and changes in vital signs and clinical laboratory tests during and following treatment [Time Frame: From first dose BGB-290 to 30 days post-dose.] [Designated as safety issue: ]

PK parameter of BGB-290 of steady state Ctrough [Time Frame: From first dose BGB-290 to 30 days post dose.] [Designated as safety issue: ]

PK parameter of BGB-290 (Cmax) [Time Frame: From first dose BGB-290 to 30 days post dose.] [Designated as safety issue: ]

Disease control rate (DCR). [Time Frame: From first dose BGB-290 to first documentation of disease progression while subject is alive, assessed up to 5 years] [Designated as safety issue: ]

Duration of response (DOR). [Time Frame: From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years] [Designated as safety issue: ]

Progression free survival (PFS) [Time Frame: From first dose BGB-290 until first documentation of disease progression or death, whichever is first, assessed up to 5 years] [Designated as safety issue: ]

Overall survival (OS) [Time Frame: From first dose BGB-290 until date of death, assessed up to 5 years] [Designated as safety issue: ]

Incidence, nature and severity of adverse events as assessed by CTCAE [Time Frame: From first dose BGB-290 to 30 days post dose.] [Designated as safety issue: ]

Number of treatment cycles, dose intensity of components of each treatment regimen, and changes in vital signs and clinical laboratory tests during and following treatment [Time Frame: From first dose BGB-290 to 30 days post-dose.] [Designated as safety issue: ]

PK parameter of BGB-290 of steady state Ctrough [Time Frame: From first dose BGB-290 to 30 days post dose.] [Designated as safety issue: ]

PK parameter of BGB-290 (Cmax) [Time Frame: From first dose BGB-290 to 30 days post-dose.] [Designated as safety issue: ]

Estimated Enrollment: 300
Study Start Date: June 2017
Estimated Study Completion Date: October 2021
Estimated Primary Completion Date: June 2021
Arms Assigned Interventions

Experimental:Arm A (Dose Escalation)

Approximately 18 subjects (newly diagnosed unmethylated GB) to receive BGB-290 and radiation therapy
Radiation:Radiation
Up to 60 Gy (total) over 6 - 7 weeks

Experimental:Arm B (Dose Escalation)

Approximately 24 subjects (newly diagnosed unmethylated GB) to receive BGB-290, radiation therapy (RT) and temozolomide (TMZ)
Drug:TMZ
TMZ

Experimental:Arm A (Dose Expansion)

Approximately 60 subjects (newly diagnosed unmethylated GB) to receive BGB-290 and radiation therapy

Experimental:Arm B (Dose Expansion)

Approximately 60 subjects (newly diagnosed unmethylated GB) to receive BGB-290, radiation therapy, and TMZ

Experimental:Arm C (Dose Escalation)

Approximately 24 subjects with recurrent/refractory methylated or unmethylated GB to receive BGB-290 and TMZ

Experimental:Arm C (Dose Expansion-Cohorts C1 and C2)

Approximately 120 subjects with recurrent/refractory GB (Cohort 1 - 60 subjects with unmethylated GB; Cohort 2 - 60 subjects with methylated GB) to receive BGB-290 and TMZ

Eligibility

Ages Eligible for Study: 99 Years-99 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria: 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:

9. No previous treatment for GB except surgery.

10. 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.

11. Documented unmethylated MGMT promoter status.

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

12. No prior systemic chemotherapy other than TMZ for GB.

13. Progressive disease > 2 months after completion of first line therapy.

14. 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.

15. 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.

16. Documentation of methylated MGMT promoter status.

Exclusion Criteria: 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.]

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03150862

Locations

  • United States, Arizona
    • Center for Neurosciences Tucson, Arizona, United States, 85718
  • United States, California
    • UCLA Neuro-Oncology Los Angeles, California, United States, 90095
    • University of California at San Francisco San Francisco, California, United States, 94143
  • United States, Colorado
    • Sarah Cannon Research Institute at Health One Denver, Colorado, United States, 80218
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02214
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • Henry Ford Health Systems Detroit, Michigan, United States, 48202
  • United States, Missouri
    • Washington University Saint Louis, Missouri, United States, 63110
  • United States, New York
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, Ohio
    • Cleveland Clinic Cleveland, Ohio, United States, 44195
    • The Ohio State University Columbus, Ohio, United States, 43210
  • United States, Oklahoma
    • University of Oklahoma Health Sciences Center (Stephenson Cancer Center) Oklahoma City, Oklahoma, United States, 73104
  • United States, Pennsylvania
    • Thomas Jefferson University Philadelphia, Pennsylvania, United States, 19107
  • United States, Tennessee
    • SCRI / Tennessee Oncology Nashville, Tennessee, United States, 37203
  • United States, Utah
    • Huntsman Cancer Center Salt Lake City, Utah, United States, 84112
  • United States, Virginia
    • University of Virginia Health Systems Charlottesville, Virginia, United States, 22903
  • Australia, New South Wales
    • Liverpool Hospital Liverpool, New South Wales, Australia, 2170
  • France,
    • Institut Gustave Roussy Villejuif, , France, 94850
  • Netherlands,
    • Erasmus University Medical Center Rotterdam, , Netherlands, 3075 EA
  • Switzerland,
    • University Hospital Zurich - Department of Neurology Zurich, , Switzerland, CH-8091

Sponsors and Collaborators

BeiGene USA, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03150862
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by BeiGene:

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

Additional relevant MeSH terms:

Glioblastoma

Nervous System Neoplasms

Central Nervous System Neoplasms

Temozolomide

Molecular Mechanisms of Pharmacological Action

Poly(ADP-ribose) Polymerase Inhibitors

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019