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

NCT03150810

Description:

This study is to evaluate the safety, efficacy and clinical activity of BGB-290 and temozolomide (TMZ) in subjects with locally advanced or metastatic solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Gastric Carcinoma
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Small Cell Lung Carcinoma
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 Subjects 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
  • NCT ID: NCT03150810

Conditions

  • Locally Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
BGB-290Arm A (Dose Escalation)
TemozolomideTMZArm A (Dose Escalation)
BGB-290Arm C (Dose Expansion)
TemozolomideTMZArm C (Dose Expansion)

Purpose

This study is to evaluate the safety, efficacy and clinical activity of BGB-290 and temozolomide (TMZ) in subjects with locally advanced or metastatic solid tumors.

Detailed Description

      This is an open-label study of BGB‑290 and temozolomide (TMZ) with a dose escalation and dose
      expansion phase. Dose escalation will evaluate safety, tolerability, preliminary efficacy,
      and PK and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) for
      the two drug combination. It is a modified 3+3 dose escalation scheme with a fixed dose of
      BGB‑290 in combination with escalating doses of TMZ. Dose expansion will evaluate the safety,
      PK profile and anti-tumor activity of BGB-290 and TMZ at a dose/schedule selected from the
      dose escalation phase. Five different solid malignancy types (n=100) will be evaluated.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (Dose Escalation)ExperimentalApproximately 25 subjects to receive continuous BGB-290 and TMZ (Days 1 - 7 of 28 day cycle).
  • BGB-290
  • Temozolomide
Arm B (Dose Escalation)ExperimentalApproximately 25 subjects to receive continuous BGB-290 and continuous TMZ (28-day cycle).
  • BGB-290
  • Temozolomide
Arm C (Dose Expansion)ExperimentalApproximately 100 subjects to receive BGB-290 and TMZ.
  • BGB-290
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria: All subjects

          1. Age ≥18 years old.

          2. Confirmed malignancy at advanced or metastatic stage.

          3. ECOG status ≤ 1.

          4. Adequate bone marrow function.

          5. Adequate renal and hepatic function.

          6. 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.

          7. Must have measurable or evaluable disease per RECIST [Dose escalation phase only]

             Additional inclusion criteria 8 - 12 are specific to tumor types in dose expansion
             phase:

          8. Ovarian cancer

               1. Previously received at least 1 line of platinum containing chemotherapy.

               2. No progression or recurrent disease in 6 months from last platinum containing
                  regimen.

          9. Triple-Negative Breast Cancer

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

         10. Prostate cancer

               1. Documented progressive disease.

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

               3. May be pre-or post-treatment with a novel androgen receptor targeted agent.

               4. Completed in ≥ 2 weeks radiation or treatment with anti-androgen agents.

         11. Ovarian, breast and prostate cancer: If homologous recombinant deficiency (HRD) or
             BRCA status unknown, need pre-screening for eligibility.

         12. Small cell lung and gastric cancer: previously received ≤ 2 prior lines of therapy.

        Exclusion Criteria: All subjects

          1. Prior exposure to a PARP inhibitor.

          2. Prior chemotherapy, biologic therapy, immunotherapy or investigational agents within 3
             weeks prior to start of study treatment.

          3. Refractory to platinum-based therapy.

          4. Toxicity of ≥ Grade 2 from prior therapy.

          5. Major surgery or significant injury ≤ 4 weeks prior to start of study treatment.

          6. History of other active malignancies within 2 years with exception of (i) adequately
             treated in situ carcinoma 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.

          7. Untreated leptomeningeal or brain metastasis.

          8. Active infection requiring systemic treatment.

          9. Known human immunodeficiency virus (HIV) or active viral hepatitis.

         10. Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease,
             ventricular arrhythmia or CVA ≤ 6 months prior to start of treatment.

         11. Active, clinically significant gastrointestinal disease.

         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.
      
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 to 28 days post-dosing.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic (PK) parameters (Cmax) of BGB-290 and TMZ.
Time Frame:From first dose BGB-290 to 30 days post-dosing.
Safety Issue:
Description:
Measure:Pharmacokinetic (PK) parameters (Tmax) of BGB-290 and TMZ.
Time Frame:From first dose BGB-290 to 30 days post-dosing.
Safety Issue:
Description:
Measure:Objective response rate (ORR) as assessed using RECIST.
Time Frame:From first dose BGB-290 to first documentation of disease progression, assessed up to 5 years.
Safety Issue:
Description:
Measure:Duration of response (DOR).
Time Frame:From first dose BGB-290 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 to first documentation of disease progression while subject is alive, assessed to up 5 years
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:From first dose BGB-290 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 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 USA, Inc.

Trial Keywords

  • Ovarian cancer
  • Triple negative breast cancer
  • Small cell lung cancer
  • Prostate cancer,
  • Gastric cancer
  • neoplasms
  • temozolomide
  • BGB-290
  • antineoplastic agents
  • alkylating, alkylating agents,
  • Poly (ADP-ribose) polymerase inhibitors
  • enzyme inhibitors

Last Updated

August 9, 2017