Clinical Trials /

First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients With Central Nervous System Metastases

NCT03653546

Description:

Primary Hypothesis The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced Non-Small Cell Lung Cancer (NSCLC) with Central Nervous System (CNS) metastasis Secondary Hypothesis The safety profile of AZD3759 is comparable to EGFR TKI first-line treatment in patients with advanced NSCLC with CNS metastasis.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients With Central Nervous System Metastases
  • Official Title: A Randomized, Open-label, Controlled, Multi-Center Phase II/III Study to Assess the Efficacy and Safety of AZD3759 vs. a Standard of Care EGFR TKI, as First Line Treatment to EGFR Mutation Positive Advanced NSCLC With CNS Metastases

Clinical Trial IDs

  • ORG STUDY ID: AZD3759-003
  • NCT ID: NCT03653546

Conditions

  • Non-small Cell Lung Cancer
  • EGFR Gene Mutation
  • Brain Metastases

Interventions

DrugSynonymsArms
AZD3759AZD3759 Group
ErlotinibTarcevaErlotinib or Gefitinib Group
GefitinibIressaErlotinib or Gefitinib Group

Purpose

Primary Hypothesis The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced Non-Small Cell Lung Cancer (NSCLC) with Central Nervous System (CNS) metastasis Secondary Hypothesis The safety profile of AZD3759 is comparable to EGFR TKI first-line treatment in patients with advanced NSCLC with CNS metastasis.

Detailed Description

      This is a Phase II/III randomized, open-label, multicenter study to compare the efficacy and
      safety of first line single-agent AZD3759 vs. Erlotinib or Gefitinib treatment in patients
      with advanced NSCLC with CNS metastases.

      Eligible patients with documented EGFR mutation+ (L858R and/or Exon 19Del) TKI-naïve advanced
      NSCLC and documented intracranial disease will be enrolled.

      Primary Objective:

      The primary objective of this study is to determine if administration of single agent AZD3759
      compared to Standard of Care (SoC) EGFR-TKI as first-line therapy results in a significant
      increase in Progression Free Survival (PFS) in the study patient population by Blinded
      Independent Central Radiological(BICR) review.

      Secondary Objectives:

      Key secondary objective for this study is to determine if AZD3759 vs. SoC EGFR TKI
      administration demonstrates additional benefit in terms of safety, Objective Response Rate
      (ORR), Disease Control Rate (DCR), Duration of Response (DoR), and overall PFS using modified
      RECIST 1.1 criteria by investigator assessment.

      Additional secondary objectives include assessment of Health Related Quality of Life (HRQoL),
      neurological function, and Overall Survival (OS).
    

Trial Arms

NameTypeDescriptionInterventions
AZD3759 GroupExperimentalAZD3759 group will receive a 300 mg twice daily dose of AZD3759
  • AZD3759
Erlotinib or Gefitinib GroupActive ComparatorSoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D
  • Erlotinib
  • Gefitinib

Eligibility Criteria

        Inclusion Criteria:

          1. Properly completed patient informed consent

          2. Male or female aged at least 18 years

          3. Histologically or cytologically confirmed diagnosis of NSCLC with activating EGFR
             mutations including L858R and/or Exon19Del. EGFR mutation status will be determined by
             local or central laboratory testing on tumour tissue or plasma utilizing a validated
             methodology which has been approved by the regulatory authority.

          4. No prior treatment with chemotherapy, EGFR-TKIs, or biological therapies that are
             considered first line treatment for advanced NSCLC.

          5. All patients must have a documented diagnosis of advanced (Stage IV) NSCLC with
             Magnetic Resonance Imaging (MRI) documented CNS metastases that include brain
             metastases (BM). BM + patients with co- existent leptomeningeal involvement are
             eligible for the study.

          6. Eligible patients are not candidates for definitive surgical resection or radiation of
             all lesions in the opinion of the treating physician.

          7. All patients must be stable without any systemic (oral or parenteral) corticosteroid
             or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled
             non-absorbable and topical corticosteroid use are permitted as indicated.

          8. Patients may have prior placement of a properly functioning CNS shunt or Ommaya
             reservoir.

          9. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no
             deterioration over the previous 2 weeks.

         10. Women of child-bearing potential and male subjects shall agree to take medically
             acceptable contraception measures while on study treatment and for 3 months following
             completion of study treatment. All women of child-bearing potential must have a
             negative blood pregnancy test at screening.

         11. (a) For Patients with measurable CNS lesions must have AT LEAST ONE site of CNS
             lesion, which was not previously irradiated, that can be accurately measured at
             baseline as ≥ 10 mm in the longest diameter by MRI and which is suitable for accurate
             repeated measurements. Measurable extracranial disease is not required. (b) For
             Patients with non-measurable CNS lesions must have AT LEAST ONE extracranial lesion,
             which has not been previously irradiated, within the screening period that can be
             accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes
             which must have short axis ≥ 15 mm) by CT/MRI and are suitable for accurate repeated
             measurement.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall PFS assessed by Blinded Independent Central Radiological
Time Frame:36 months
Safety Issue:
Description:To assess if first line treatment with AZD3759 results in significant overall PFS efficacy compared to Gefitinib or Erlotinib as determined by Blinded Independent Central Radiological (BICR) review using modified RECIST 1.1.

Secondary Outcome Measures

Measure:Overall PFS assess by investigator
Time Frame:36 months
Safety Issue:
Description:Investigator assessment of PFS using modified RECIST 1.1
Measure:Intracranial PFS (iPFS) assessed by investigator
Time Frame:36 months
Safety Issue:
Description:Intracranial PFS (iPFS) assessed by investigator using modified RECIST 1.1
Measure:Intracranial PFS (iPFS) assessed by BICR
Time Frame:36 months
Safety Issue:
Description:Intracranial PFS (iPFS) assessed by Blinded Independent Central Radiological (BICR) using modified RECIST 1.1
Measure:Extracranial PFS (ePFS) assessed by investigator
Time Frame:36 months
Safety Issue:
Description:Extracranial PFS (ePFS) assessed by investigator using modified RECIST 1.1
Measure:Extracranial PFS (ePFS) assessed by BICR
Time Frame:36 months
Safety Issue:
Description:Extracranial PFS (ePFS) assessed by Blinded Independent Central Radiological (BICR) using modified RECIST 1.1
Measure:Objective Response Rate (ORR) assessed by investigator using modified RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Objective Response Rate (ORR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using modified RECIST 1.1
Measure:Disease Control Rate (DCR) assessed by investigator using modified RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Disease Control Rate (DCR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using modified RECIST 1.1
Measure:Duration of Response (DoR) assessed by investigator using modified RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Duration of Response (DoR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using modified RECIST 1.1
Measure:Overall ORR assessed by investigator using modified RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Overall ORR assessed by investigator using modified RECIST 1.1
Measure:Overall DCR assessed by investigator using modified RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Overall DCR assessed by investigator using modified RECIST 1.1
Measure:Overall DoR assessed by investigator using modified RECIST 1.1
Time Frame:36 months
Safety Issue:
Description:Overall DoR assessed by investigator using modified RECIST 1.1
Measure:ORR for Intracranial lesions assessed by investigator using modified RANO
Time Frame:36 months
Safety Issue:
Description:ORR for Intracranial lesions assessed by investigator using modified RANO
Measure:DCR for Intracranial lesions assessed by investigator using modified RANO
Time Frame:36 months
Safety Issue:
Description:DCR for Intracranial lesions assessed by investigator using modified RANO
Measure:DoR for Intracranial lesions assessed by investigator using modified RANO
Time Frame:36 months
Safety Issue:
Description:DoR for Intracranial lesions assessed by investigator using modified RANO
Measure:Overall Survival
Time Frame:36 months
Safety Issue:
Description:Overall Survival
Measure:Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).
Time Frame:36 months
Safety Issue:
Description:The 30-items questionnaire measures cancer patients' functioning and symptoms. The scale range of EORTC QLQ-C30 is 30-126. Lower values represent a better outcome.
Measure:Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BN20 (EORTC QLQ-BN20).
Time Frame:36 months
Safety Issue:
Description:The 20-items questionnaire was used among brain cancer patients. The scale range of EORTC BN20 is 20-80. Lower values represent a better outcome.
Measure:Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)
Time Frame:36 months
Safety Issue:
Description:Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)
Measure:Neurological function improvement rate assessed by modified RANO criteria
Time Frame:36 months
Safety Issue:
Description:Neurological function improvement rate assessed by modified RANO criteria
Measure:Number of participants with treatment-related Adverse Events as assessed by CTCAE v5.0
Time Frame:36 months
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measure:Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0
Time Frame:36 months
Safety Issue:
Description:Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0
Measure:Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0
Time Frame:36 months
Safety Issue:
Description:Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0
Measure:Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0
Time Frame:36 months
Safety Issue:
Description:Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0
Measure:Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0
Time Frame:36 months
Safety Issue:
Description:Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0
Measure:Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.
Time Frame:36 months
Safety Issue:
Description:Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.
Measure:Systolic and Diastolic Blood Pressure assessed during the study period.
Time Frame:36 months
Safety Issue:
Description:Systolic and Diastolic Blood Pressure assessed during the study period.
Measure:Pulse rate assessed during the study period.
Time Frame:36 months
Safety Issue:
Description:Pulse rate to assessed during the study period.
Measure:Body temperature assessed during the study period.
Time Frame:36 months
Safety Issue:
Description:Body temperature assessed during the study period.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Alpha Biopharma (Jiangsu) Co., Ltd.

Trial Keywords

  • Central Nervous System Metastases
  • Respiratory Tract Diseases
  • EGFR
  • Exon 19Del
  • L858R
  • Lung Neoplasm
  • Carcinoma, Non-Small-Cell Lung
  • Neoplasms

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