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

• Register: ClinicalTrials.gov
• Last refreshed on: 26 April 2021
• Main ID: NCT03150862
• Date of registration: 08/05/2017
• Prospective Registration: Yes
• Primary sponsor: BeiGene USA, Inc.
• Public title: A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma
• Scientific 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
• Date of first enrolment: August 1, 2017
• Target sample size: 116
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03150862
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, France, Netherlands, Switzerland, United States

Contacts

• Name: Katie Wood, RN
• Affiliation: BeiGene

Key inclusion & exclusion criteria

Key Inclusion Criteria: All participants

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. Eastern Cooperative Oncology Group (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.

Participants 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.

Participants 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

Participants 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

Key Exclusion Criteria: All participants

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 Cerebrovascular Accident (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 participant'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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Brain and Central Nervous System Tumors

Intervention(s)

Drug: Pamiparib

Drug: TMZ

Radiation: Radiation

Primary Outcome(s)

Phase 1b: Number of treatment cycles (Arm C only), 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 + RT +/- TMZ to 30 days post final dose of pamiparib +/- RT or TMZ]

Phase 1b: Incidence and nature of dose limiting toxicities (DLTs) as assessed by CTCAE [Time Frame: Time Frame: From first dose Pamiparib + RT +/- TMZ to up to 10 weeks post-dose (Arms A and B) . From first dose Pamiparib +TMZ to 28 days post-dose (Arm Cv)]

Phase 2 Arm A [Pamiparib + RT] and Arm B [Pamiparib + RT + TMZ]: Modified disease control rate (mDCR) using modified Response Assessment in Neuro-oncology (mRANO) [Time Frame: From first dose Pamiparib to first documentation of progression while participant is alive, assessed up to 5 years.]

Phase 2 Arm C [Pamiparib + TMZ]: Objective response rate (ORR) using mRANO [Time Frame: Time Frame: From first dose of Pamiparib to first documentation of progression while participant is alive assessed up to 5 years.]]

Phase 1b: Incidence, nature and severity of adverse events as assessed by CTCAE [Time Frame: From first dose Pamiparib + RT +/- TMZ to 30 days post final dose of pamiparib +/- RT or TMZ]

Secondary Outcome(s)

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).]

Disease control rate [Time Frame: From first dose Pamiparib to first documentation of disease progression while participant is alive assessed up to 5 years.]

Clinical benefit rate (CBR) [Time Frame: From first dose Pamiparib to first documentation of disease progression while participant is alive assessed up to 5 years.]

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).]

Overall survival (OS) [Time Frame: From first dose Pamiparib until date of death, assessed up to 5 years.]

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]

Objective response rate (ORR) [Time Frame: From first dose Pamiparib to first documentation of disease progression while participant is alive assessed up to 5 years.]

Duration of response (DOR) [Time Frame: From first documentation of CR or PR to first documentation of progression or death, assessed up to 5 years]

PK parameter of Pamiparib of steady state Ctrough [Time Frame: From first dose Pamiparib to 30 days post dose.]

Progression free survival (PFS). [Time Frame: From first dose Pamiparib to first documentation of progression or death, assessed up to 5 years]

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]

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.]

Secondary ID(s)

BGB-290-104

2017-001554-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors