Description:
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 EGFR mutation positive non-small cell
lung cancer (NSCLC) with Central Nervous System (CNS) metastasis
Title
- Brief Title: First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients With Central Nervous System (CNS) 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
Drug | Synonyms | Arms |
---|
AZD3759 | | AZD3759 Group |
Erlotinib | Tarceva | Erlotinib or Gefitinib Group |
Gefitinib | Iressa | Erlotinib or Gefitinib Group |
Purpose
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 EGFR mutation positive non-small cell
lung cancer (NSCLC) with Central Nervous System (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 EGFR mutation positive 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.
Trial Arms
Name | Type | Description | Interventions |
---|
AZD3759 Group | Experimental | AZD3759 group will receive a 200 mg twice daily dose of AZD3759 | |
Erlotinib or Gefitinib Group | Active Comparator | SoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D | |
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: | 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 PFS efficacy compared to Gefitinib or Erlotinib as determined by Blinded Independent Central Radiological (BICR) review using RECIST 1.1. |
Secondary Outcome Measures
Measure: | PFS assess by investigator |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Investigator assessment of PFS using RECIST 1.1 |
Measure: | Intracranial PFS (iPFS) assessed by investigator |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Intracranial PFS (iPFS) assessed by investigator using 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 RECIST 1.1 |
Measure: | Extracranial PFS (ePFS) assessed by investigator |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Extracranial PFS (ePFS) assessed by investigator using 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 RECIST 1.1 |
Measure: | Objective Response Rate (ORR) assessed by investigator using 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 RECIST 1.1 |
Measure: | Disease Control Rate (DCR) assessed by investigator using 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 RECIST 1.1 |
Measure: | Duration of Response (DoR) assessed by investigator using 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 RECIST 1.1 |
Measure: | Overall ORR assessed by investigator using RECIST 1.1 |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Overall ORR assessed by investigator using RECIST 1.1 |
Measure: | Overall DCR assessed by investigator using RECIST 1.1 |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Overall DCR assessed by investigator using RECIST 1.1 |
Measure: | Overall DoR assessed by investigator using RECIST 1.1 |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Overall DoR assessed by investigator using RECIST 1.1 |
Measure: | ORR for Intracranial lesions assessed by investigator using RANO-BM |
Time Frame: | 36 months |
Safety Issue: | |
Description: | ORR for Intracranial lesions assessed by investigator using RANO-BM |
Measure: | DCR for Intracranial lesions assessed by investigator using RANO-BM |
Time Frame: | 36 months |
Safety Issue: | |
Description: | DCR for Intracranial lesions assessed by investigator using RANO-BM |
Measure: | DoR for Intracranial lesions assessed by investigator using RANO-BM |
Time Frame: | 36 months |
Safety Issue: | |
Description: | DoR for Intracranial lesions assessed by investigator using RANO-BM |
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 RANO-BM criteria |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Neurological function improvement rate assessed by RANO-BM 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. |
Measure: | PFS assess by BICR |
Time Frame: | 36 months |
Safety Issue: | |
Description: | Blinded Independent Central Radiological (BICR) assessment of PFS using modified RECIST 1.1. |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not 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
Last Updated
July 12, 2021