Clinical Trials /

Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors

NCT03150810

Description:

The primary objective of this study is to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the antitumor activity of pamiparib in combination with TMZ.

Related Conditions:
  • Breast Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Small Cell Lung Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1b Study to Assess the Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BGB-290-103
  • SECONDARY ID: 2017-001553-14
  • NCT ID: NCT03150810

Conditions

  • Locally Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
PamiparibBGB-290Arm A (Dose Escalation) TMZ Pulse Dosing
TemozolomideTMZ, temodarArm A (Dose Escalation) TMZ Pulse Dosing

Purpose

The primary objective of this study is to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the antitumor activity of pamiparib in combination with TMZ.

Trial Arms

NameTypeDescriptionInterventions
Arm A (Dose Escalation) TMZ Pulse DosingExperimentalParticipants receive continuous BGB-290 and escalating flat doses of 40mg, 80mg, 100mg, 120mg (as 20 mg capsules) daily administered orally up to the maximum tolerated dose (MTD) of TMZ on Days 1 - 7 of a 28-day cycle.
  • Pamiparib
  • Temozolomide
Arm B (Dose Escalation) TMZ Continuous DosingExperimentalParticipants receive continuous BGB-290 and escalating flat doses of 40mg, 80mg, 100mg, 120mg (as 20 mg capsules) daily administered orally up to the maximum tolerated dose (MTD) of TMZ on Days 1 - 28 of a 28-day cycle.
  • Pamiparib
  • Temozolomide
Dose Expansion, 6 cohortsExperimentalParticipants receive continuous BGB-290 and TMZ at the recommended phase 2 dose (RP2D) and schedule in 28 day cycles
  • Pamiparib
  • Temozolomide

Eligibility Criteria

        Key Inclusion Criteria:

          1. Age ≥18 years old with advanced or metastatic stage solid tumors

          2. Eastern Cooperative Oncology Group (ECOG) status ≤ 1 and measurable disease per RECIST
             V1.1 (except for participants in dose escalation and prostate cancer participants)

          3. Additional inclusion criteria for dose expansion cohorts:

        Participants with homologous recombination deficiency (HRD+) or known BRCA mutant Ovarian
        cancer

        a. Previously received at least 1 line of platinum containing chemotherapy and No
        progression or recurrent disease in 6 months from last platinum containing regimen.
        Participants with HRD+ or known breast cancer susceptibility gene (BRCA) mutant
        Triple-Negative Breast Cancer

        a. 0 - 1 prior platinum-containing regimen (any treatment setting) and received ≤ 3 prior
        regimens (advanced or metastatic setting).

        Participants with HRD+ or known BRCA mutant Prostate cancer

          1. Chemotherapy-naïve or previously received ≤2 taxane-based regimens.

          2. May have pre-or post-treatment with a novel androgen receptor targeted agent.
             Participants Small cell lung and gastric cancer

        a. Previously received ≤ 2 prior lines of therapy. Participants with HRD+ NSCLC, head and
        neck cancer, esophageal cancer and soft tissue sarcomas

          1. Must have tumors with with HRD+ as centrally determined

          2. Must have received at least 1 but not more than 3 prior lines of therapy.

        Treatment naïve patients with soft tissue sarcoma might be allowed if standard of care
        therapy is not suitable or available.

        Key Exclusion Criteria: All participants

          1. Prior exposure to a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.

          2. Refractory to platinum-based therapy.

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and nature of dose limiting toxicities (DLTs) as assessed by CTCAE.
Time Frame:From first dose BGB-290 and TMZ to 28 days post-dosing
Safety Issue:
Description:

Secondary Outcome Measures

Measure:maximum observed plasma concentration (Cmax) of BGB-290 and TMZ.
Time Frame:From first dose BGB-290 and TMZ to 30 days post-dosing
Safety Issue:
Description:
Measure:lowest concentration reached before the next dose administered (Ctrough) of BGB-290 and TMZ.
Time Frame:From first dose BGB-290 and TMZ to 30 days post-dosing
Safety Issue:
Description:
Measure:time to reach maximum (peak) plasma concentration (Tmax) of BGB-290 and TMZ.
Time Frame:From first dose BGB-290 and TMZ to 30 days post-dosing
Safety Issue:
Description:
Measure:Duration of response (DOR).
Time Frame:From first dose BGB-290 and TMZ to first documentation of disease progression, assessed up to 5 years
Safety Issue:
Description:
Measure:Disease control rate (DCR)
Time Frame:From first dose BGB-290 and TMZ to first documentation of disease progression while participant is alive, assessed to up 5 years
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:From first dose BGB-290 and TMZ to first documentation of disease progression or death, whichever is first, assessed up to 5 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From first dose BGB-290 and TMZ until date of death, assessed up to 5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BeiGene

Trial Keywords

  • Ovarian cancer
  • Triple negative breast cancer
  • Small cell lung cancer
  • Prostate cancer,
  • Gastric cancer
  • temozolomide
  • BGB-290
  • antineoplastic agents
  • alkylating, alkylating agents,
  • Poly (ADP-ribose) polymerase inhibitors
  • enzyme inhibitors
  • Head and neck cancer
  • Esophageal cancer
  • Soft tissue sarcoma
  • Non small cell lung cancer
  • pamiparib

Last Updated

September 10, 2020