First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients with Central Nervous System (CNS) Metastases
- Conditions
- EGFR Gene MutationNon-small Cell Lung CancerBrain Metastases
- Interventions
- Registration Number
- NCT03653546
- Lead Sponsor
- Alpha Biopharma (Jiangsu) Co., Ltd.
- Brief Summary
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 492
- Properly completed patient informed consent
- Male or female aged at least 18 years
- 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.
- No prior treatment with chemotherapy, EGFR-TKIs, or biological therapies that are considered first line treatment for advanced NSCLC.
- 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.
- Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
- 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.
- Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks.
- 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.
- (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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD3759 Group AZD3759 AZD3759 group will receive a 200 mg twice daily dose of AZD3759 Erlotinib or Gefitinib Group Erlotinib SoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D Erlotinib or Gefitinib Group Gefitinib SoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D
- Primary Outcome Measures
Name Time Method PFS assessed by Blinded Independent Central Radiological 48 months 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
Name Time Method Overall ORR assessed by investigator using RECIST 1.1 48 months Overall ORR assessed by investigator using RECIST 1.1
DoR for Intracranial lesions assessed by investigator using RANO-BM 48 months DoR for Intracranial lesions assessed by investigator using RANO-BM
Extracranial PFS (ePFS) assessed by investigator 48 months Extracranial PFS (ePFS) assessed by investigator using RECIST 1.1
Disease Control Rate (DCR) assessed by investigator using RECIST 1.1 48 months Disease Control Rate (DCR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1
Duration of Response (DoR) assessed by investigator using RECIST 1.1 48 months Duration of Response (DoR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1
Overall DCR assessed by investigator using RECIST 1.1 48 months Overall DCR assessed by investigator using RECIST 1.1
Body temperature assessed during the study period. 48 months Body temperature assessed during the study period.
Overall Survival 48 months Overall Survival
Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE) 48 months Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)
Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0 48 months Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0
Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0 48 months Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0
PFS assess by BICR 48 months Blinded Independent Central Radiological (BICR) assessment of PFS using modified RECIST 1.1.
Intracranial PFS (iPFS) assessed by BICR 48 months Intracranial PFS (iPFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1
Extracranial PFS (ePFS) assessed by BICR 48 months Extracranial PFS (ePFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1
Overall DoR assessed by investigator using RECIST 1.1 48 months Overall DoR assessed by investigator using RECIST 1.1
ORR for Intracranial lesions assessed by investigator using RANO-BM 48 months ORR for Intracranial lesions assessed by investigator using RANO-BM
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BN20 (EORTC QLQ-BN20). 48 months 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.
Neurological function improvement rate assessed by RANO-BM criteria 48 months Neurological function improvement rate assessed by RANO-BM criteria
Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0 48 months Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0
Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period. 48 months Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.
PFS assess by investigator 48 months Investigator assessment of PFS using RECIST 1.1
Intracranial PFS (iPFS) assessed by investigator 48 months Intracranial PFS (iPFS) assessed by investigator using RECIST 1.1
Objective Response Rate (ORR） assessed by investigator using RECIST 1.1 48 months Objective Response Rate (ORR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1
DCR for Intracranial lesions assessed by investigator using RANO-BM 48 months DCR for Intracranial lesions assessed by investigator using RANO-BM
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). 48 months 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.
Number of participants with treatment-related Adverse Events as assessed by CTCAE v5.0 48 months Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0 48 months Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0
Systolic and Diastolic Blood Pressure assessed during the study period. 48 months Systolic and Diastolic Blood Pressure assessed during the study period.
Pulse rate assessed during the study period. 48 months Pulse rate to assessed during the study period.
Trial Locations
- Locations (6)
China site
🇨🇳Tianjin, China
China site 0123
🇨🇳Jinan, Shandong, China
Korea Site
🇰🇷Seoul, Korea, Republic of
Korea site
🇰🇷Ulsan, Korea, Republic of
Singapore site
🇸🇬Singapore, Singapore
Taiwan site
🇨🇳Taoyuan, Taiwan