Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03150862
Recruitment Status : Active, not recruiting
First Posted : May 12, 2017
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE May 8, 2017
First Posted Date  ICMJE May 12, 2017
Last Update Posted Date November 7, 2019
Actual Study Start Date  ICMJE August 1, 2017
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
  • Incidence and nature of dose limiting toxicities (DLTs) as assessed by CTCAE [ Time Frame: From first dose Pamiparib to 10 weeks post-dose (Arms A and B). From first dose Pamiparib to 28 days post-dose (Arm C). ]
  • Incidence, nature and severity of adverse events as assessed by CTCAE [ Time Frame: From first dose Pamiparib to 30 days post final dose of pamiparib +/- RT or TMZ. ]
  • 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 Pamiparib to 30 days post final dose of pamiparib +/- RT or TMZ. ]
  • Phase 2 Arm A [Pamiparib + RT] and Arm B [Pamiparib + RT + TMZ]: Modified disease control rate (mDCR) using mRANO [ Time Frame: From first dose Pamiparib to first documentation of progression while subject is alive, assessed up to 5 years. ]
    Modified disease control rate (DCR) using mRANO
  • Phase 2 Arm C [Pamiparib + TMZ]: Objective response rate (ORR) using mRANO [ Time Frame: From first dose of Pamiparib to first documentation of progression assessed up to 5 years. ]
    Objective response rate (ORR) using mRANO
Original Primary Outcome Measures  ICMJE
 (submitted: May 10, 2017)
  • 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). ]
  • Incidence, nature and severity of adverse events as assessed by CTCAE [ Time Frame: From first dose BGB-290 to 30 days post-dose. ]
  • 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. ]
  • 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. ]
    Modified disease control rate (DCR) using mRANO
  • 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. ]
    Objective response rate (ORR) using mRANO
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
  • Pharmacokinetic (PK) parameters of Pamiparib of steady state Ctrough [ Time Frame: From first dose Pamiparib to 30 days post-final dose of pamiparib +/- RT or TMZ. ]
  • Modified disease control rate (DCR). (Arms A and B) [ Time Frame: From first dose Pamiparib to first documentation of disease progression while subject is alive assessed up to 5 years ]
  • Disease control rate (Arm C) [ Time Frame: From first dose Pamiparib to first documentation of disease progression while subject is alive assessed up to 5 years. ]
  • Objective response rate (ORR) [ Time Frame: From first dose Pamiparib to first documentation of disease progression while subject is alive assessed up to 5 years. ]
  • Clinical benefit rate (CBR). [ Time Frame: From first dose Pamiparib to first documentation of disease progression while subject is alive assessed up to 5 years. ]
  • Duration of response (DOR). [ Time Frame: From first dose Pamiparib to first documentation of progression while subject is alive, assessed up to 5 years. ]
  • Progression free survival (PFS). [ Time Frame: From first dose Pamiparib to first documentation of progression while subject is alive, assessed up to 5 years. ]
  • Overall survival (OS) [ Time Frame: From first dose Pamiparib until date of death, assessed up to 5 years. ]
  • Objective response rate (ORR). [ Time Frame: From the first dose Pamiparib to first documentation of disease progression, assessed up to 5 years. ]
    Phase 2 (Arm A and Arm B)
  • Clinical benefit rate (CBR) [ Time Frame: From first dose Pamiparib to first documentation of disease progression, assessed up to 5 years. ]
    Phase 2 (Arm A and Arm B)
  • Duration of response (DOR) [ Time Frame: From first dose Pamiparib to first documentation of disease progression, assessed up to 5 years. ]
    Phase 2 (Arm A and Arm B)
  • Progression free survival (PFS) [ Time Frame: From first dose Pamiparib to first documentation of disease progression, assessed up to 5 years. ]
    Phase 2 (Arm A and Arm B)
  • Overall survival (OS) [ Time Frame: From first dose Pamiparib + RT +/- TMZ until date of death, assessed up to 5 years. ]
    Phase 2 (Arm A and Arm B)
  • Incidence, nature and severity of adverse events as assessed by CTCAE [ Time Frame: From first dose Pamiparib + RT +/- TMZ to 30 days post- last dose of pamiparib or RT whichever is later ]
    Phase 2 (Arm A and Arm B)
  • Length of treatment, dose intensity of components of each treatment , and changes in vital signs and clinical laboratory tests during and following treatment [ Time Frame: From first dose Pamiparib + RT +/- TMZ to 30 days post- last dose of pamiparib or RT whichever is later ]
    Phase 2 (Arm A and Arm B)
  • PK parameter of Pamiparib of steady state Ctrough [ Time Frame: From first dose Pamiparib to 30 days post dose. ]
    Phase 2 (Arm A and Arm B)
  • PK parameter of Pamiparib (Cmax) [ Time Frame: From first dose Pamiparib to 30 days post dose. ]
    Phase 2 (Arm A and Arm B)
  • Disease control rate (DCR). [ Time Frame: From first dose Pamiparib + RT +/- TMZ to first documentation of progression while subject is alive, assessed up to 5 years. ]
    Phase 2 (Arm C)
  • Duration of response (DOR). [ Time Frame: From first dose of Pamiparib to first documentation of disease progression, assessed up to 5 years. ]
    Phase 2 (Arm C)
  • Progression free survival (PFS) [ Time Frame: From first dose of Pamiparib to first documentation of disease progression or death, assessed up to 5 years. ]
    Phase 2 (Arm C)
  • Overall survival (OS) [ Time Frame: From first dose Pamiparib until date of death, assessed up to 5 years. ]
    Phase 2 (Arm C)
  • Incidence, nature and severity of adverse events as assessed by CTCAE [ Time Frame: From first dose Pamiparib + TMZ to 30 days post last dose Pamiparib or TMZ, whichever is later). ]
    Phase 2 (Arm C)
  • 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 Pamiparib + TMZ to 30 days post last dose Pamiparib or TMZ (whichever is later). ]
    Phase 2 (Arm C)
  • PK parameter of Pamiparib of steady state Ctrough [ Time Frame: From first dose Pamiparib to 30 days post dose. ]
    Phase 2 (Arm C)
  • PK parameter of Pamiparib (Cmax) [ Time Frame: From first dose Pamiparib to 30 days post-dose. ]
    Phase 2 (Arm C)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2017)
  • Pharmacokinetic (PK) parameters of BGB-290 of steady state Ctrough [ Time Frame: From first dose BGB-290 to 30 days post-dose. ]
  • 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 ]
  • 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 ]
  • Objective response rate (ORR) [ Time Frame: From first dose BGB-290 to first documentation of disease progression assessed up to 5 years ]
  • Clinical benefit rate (CBR). [ Time Frame: From first dose BGB-290 to first documentation of disease progression assessed up to 5 years ]
  • Duration of response (DOR). [ Time Frame: From first dose BGB-290 to first documentation of disease progression assessed up to 5 years. ]
  • 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 ]
  • Overall survival (OS) [ Time Frame: From first dose BGB-290 until date of death, assessed up to 5 years ]
  • Objective response rate (ORR). [ Time Frame: From the first dose BGB-290 to first documentation of disease progression, assessed up to 5 years ]
    Phase 2 (Arm A and Arm B)
  • Clinical benefit rate (CBR) [ Time Frame: From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years ]
    Phase 2 (Arm A and Arm B)
  • Duration of response (DOR) [ Time Frame: From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years ]
    Phase 2 (Arm A and Arm B)
  • 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 ]
    Phase 2 (Arm A and Arm B)
  • Overall survival (OS) [ Time Frame: From first dose BGB-290 until date of death, assessed up to 5 years ]
    Phase 2 (Arm A and Arm B)
  • Incidence, nature and severity of adverse events as assessed by CTCAE [ Time Frame: From first dose BGB-290 to 30 days post dose. ]
    Phase 2 (Arm A and Arm B)
  • 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. ]
    Phase 2 (Arm A and Arm B)
  • PK parameter of BGB-290 of steady state Ctrough [ Time Frame: From first dose BGB-290 to 30 days post dose. ]
    Phase 2 (Arm A and Arm B)
  • PK parameter of BGB-290 (Cmax) [ Time Frame: From first dose BGB-290 to 30 days post dose. ]
    Phase 2 (Arm A and Arm B)
  • 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 ]
    Phase 2 (Arm C)
  • Duration of response (DOR). [ Time Frame: From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years ]
    Phase 2 (Arm C)
  • 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 ]
    Phase 2 (Arm C)
  • Overall survival (OS) [ Time Frame: From first dose BGB-290 until date of death, assessed up to 5 years ]
    Phase 2 (Arm C)
  • Incidence, nature and severity of adverse events as assessed by CTCAE [ Time Frame: From first dose BGB-290 to 30 days post dose. ]
    Phase 2 (Arm C)
  • 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. ]
    Phase 2 (Arm C)
  • PK parameter of BGB-290 of steady state Ctrough [ Time Frame: From first dose BGB-290 to 30 days post dose. ]
    Phase 2 (Arm C)
  • PK parameter of BGB-290 (Cmax) [ Time Frame: From first dose BGB-290 to 30 days post-dose. ]
    Phase 2 (Arm C)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Subjects With Newly Diagnosed or Recurrent Glioblastoma
Official Title  ICMJE 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
Brief Summary This study is to evaluate the safety, efficacy and clinical activity of Pamiparib in combination with radiation therapy (RT) and/or temozolomide (TMZ) in subjects with newly diagnosed or recurrent/refractory glioblastoma.
Detailed Description

An open‑label, multiple‑dose, dose-escalation study to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of Pamiparib in combination with radiation therapy (RT) and/or TMZ.

In dose escalation/Phase 1b, Pamiparib will be combined with RT (Arm A) or RT and TMZ (Arm B) in subjects with newly diagnosed unmethylated glioblastoma (GBM) and in Arm C of the study Pamiparib will be combined with TMZ in subjects with methylated or unmethylated recurrent/refractory GBM.

The dose expansion/Phase 2 phase will enroll up to 4 cohorts: subjects with newly diagnosed unmethylated GBM in Arms A and B, and 2 cohorts of subjects with recurrent/refractory GBM grouped by MGMT status - unmethylated or methylated - in Arm C.

Subjects in Arms A and B are treated until completion of RT and subjects in Arm C may continue treatment in the absence of safety concerns and disease progression.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
No Masking
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • Drug: BGB-290
    BGB-290
    Other Name: Pamiparib
  • Drug: TMZ
    TMZ
  • Radiation: Radiation
    Up to 60 Gy (total) over 6 - 7 weeks
Study Arms  ICMJE
  • Experimental: Arm A (Dose Escalation)
    Patients with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.
    Interventions:
    • Drug: BGB-290
    • Radiation: Radiation
  • Experimental: Arm B (Dose Escalation)
    Patients with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ).
    Interventions:
    • Drug: BGB-290
    • Drug: TMZ
    • Radiation: Radiation
  • Experimental: Arm A (Dose Expansion)
    Patients with newly diagnosed unmethylated GBM will receive Pamiparib and radiation therapy.
    Interventions:
    • Drug: BGB-290
    • Radiation: Radiation
  • Experimental: Arm B (Dose Expansion)
    Patients with newly diagnosed unmethylated GBM will receive Pamiparib, radiation therapy (RT) and temozolomide (TMZ).
    Interventions:
    • Drug: BGB-290
    • Drug: TMZ
    • Radiation: Radiation
  • Experimental: Arm C (Dose Escalation)
    Patients with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.
    Interventions:
    • Drug: BGB-290
    • Drug: TMZ
  • Experimental: Arm C (Dose Expansion-Cohorts C1 and C2)
    Patients with recurrent/refractory methylated or unmethylated GBM will receive Pamiparib and TMZ.
    Interventions:
    • Drug: BGB-290
    • Drug: TMZ
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 12, 2019)
116
Original Estimated Enrollment  ICMJE
 (submitted: May 10, 2017)
300
Estimated Study Completion Date  ICMJE October 31, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: All subjects

  1. Age ≥ 18 years old.
  2. Confirmed diagnosis of glioblastoma (WHO Grade IV).
  3. Agreement to provide archival tumor tissue for exploratory biomarker analysis
  4. Ability to undergo serial MRIs.
  5. ECOG status ≤ 1.
  6. Adequate hematologic and end-organ 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 6 months after last dosing.
  8. Ability to swallow whole capsules.

    Subjects in Arms A and B (not Arm C) must meet inclusion criteria # 9 - 11:

  9. No previous treatment for GBM 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 Escalation (Phase 1b) must meet inclusion criteria # 12 - 15:

  12. Documentation of MGMT promoter status
  13. No prior systemic chemotherapy other than TMZ for GBM.
  14. Histologically confirmed secondary glioblastoma
  15. Disease that is evaluable or measurable as defined by RANO criteria

    Subjects in Arm C Expansion (Phase 2), must meet criteria # 16 - 18:

  16. Histologically confirmed de novo (primary) glioblastoma with unequivocal first progressive disease (PD) after RT with concurrent/adjuvant TMZ chemotherapy
  17. Disease that is measurable as defined by RANO criteria
  18. Documentation of 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. Active infection requiring systemic treatment.
  6. Known human immunodeficiency virus (HIV) or active viral hepatitis.
  7. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or CVA ≤ 6 months prior to start of treatment.
  8. Active clinically significant gastrointestinal disease.
  9. Active bleeding disorder ≤ 6 months prior to start of treatment.
  10. Need for therapeutic anti-coagulation with heparin, warfarin or other anticoagulants.
  11. Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
  12. Pregnant or nursing females.
  13. Significant intercurrent illness that may result in subject's death prior to death from glioblastoma.

    Arms B and C Only:

  14. Known hypersensitivity to any component of TMZ or decarbazine (DTIC).
  15. Have hereditary problems of galactose intolerance
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Netherlands,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03150862
Other Study ID Numbers  ICMJE BGB-290-104
2017-001554-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Katie Wood, RN BeiGene
PRS Account BeiGene
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP