Non-small Cell Lung Cancer Clinical Trial
— BMOfficial 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
Verified date | November 2022 |
Source | Alpha Biopharma (Jiangsu) Co., Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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
Status | Completed |
Enrollment | 492 |
Est. completion date | July 12, 2022 |
Est. primary completion date | July 12, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
China | China site | Beijing | |
China | China site | Beijing | |
China | China site | Beijing | |
China | China site | Beijing | |
China | China site | Changchun | Jilin |
China | China site | Changchun | Jilin |
China | China site | Changsha | Hunan |
China | China site | Chengdu | Sichuan |
China | China site | Chongqing | |
China | China site | Chongqing | |
China | China site | Chongqing | |
China | China site | Fuzhou | Fujian |
China | China site | Guangzhou | Guangdong |
China | China site | Guangzhou | Guangdong |
China | China site | Haerbin | Heilongjiang |
China | China site | Hangzhou | Zhejiang |
China | China site | Hangzhou | Zhejiang |
China | China site | Hangzhou | Zhejiang |
China | China site | Hefei | Anhui |
China | China site 0123 | Jinan | Shandong |
China | China site | Kunming | Yunnan |
China | China site | Linyi | Shandong |
China | China site | Nanjing | Jiangsu |
China | China site | Nanjing | Jiangsu |
China | China site | Shanghai | |
China | China site | Shanghai | |
China | China site | Suzhou | Jiangsu |
China | China site | Tianjin | |
China | China site | Weifang | Shandong |
China | China site | Wuhan | Hubei |
China | China site | Wuhan | Hubei |
China | China site | Wuhan | Hubei |
China | China site | Wuxi | Jiangsu |
China | China site | Xi'an | Shaanxi |
China | China site | Xiamen | Fujian |
China | China site | Xuzhou | Jiangsu |
China | China site | Yangzhou | Jiangsu |
China | China site | Yantai | Shandong |
China | China site | Yichang | Hubei |
China | China site | Zhengzhou | Henan |
China | China site | Zhengzhou | Henan |
Korea, Republic of | Korea Site | Chungbuk | |
Korea, Republic of | Korea site | Daegu | |
Korea, Republic of | Korea site | Gyeonggi-do | |
Korea, Republic of | Korea site | Gyeongsang | |
Korea, Republic of | Korea site | Incheon | |
Korea, Republic of | Korea Site | Seoul | |
Korea, Republic of | Korea site | Seoul | |
Korea, Republic of | Korea Site | Seoul | |
Korea, Republic of | Korea site | Seoul | |
Korea, Republic of | Korea site | Seoul | |
Korea, Republic of | Korea site | Suwon | |
Korea, Republic of | Korea site | Ulsan | |
Singapore | Singapore site | Singapore | |
Taiwan | Taiwan site | Taichung | |
Taiwan | Taiwan site | Tainan | |
Taiwan | Taiwan site | Taipei | |
Taiwan | Taiwan site | Taoyuan |
Lead Sponsor | Collaborator |
---|---|
Alpha Biopharma (Jiangsu) Co., Ltd. |
China, Korea, Republic of, Singapore, Taiwan,
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. — View Citation
Barajas RF Jr, Cha S. Imaging diagnosis of brain metastasis. Prog Neurol Surg. 2012;25:55-73. doi: 10.1159/000331174. Epub 2012 Jan 6. Review. — View Citation
Deeken JF, Löscher W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007 Mar 15;13(6):1663-74. Review. — View Citation
Gow CH, Chien CR, Chang YL, Chiu YH, Kuo SH, Shih JY, Chang YC, Yu CJ, Yang CH, Yang PC. Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response. Clin Cancer Res. 2008 Jan 1;14(1):162-8. doi: 10.1158/1078-0432.CCR-07-1468. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Pop-PK analysis | Population pharmacokinetic analysis | 48 months | |
Other | Exposure-Response analysis | explore the correlation in exposure and efficacy, exposure and safety in the Study | 48 months | |
Primary | PFS assessed by Blinded Independent Central Radiological | 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. | 48 months | |
Secondary | PFS assess by investigator | Investigator assessment of PFS using RECIST 1.1 | 48 months | |
Secondary | Intracranial PFS (iPFS) assessed by investigator | Intracranial PFS (iPFS) assessed by investigator using RECIST 1.1 | 48 months | |
Secondary | Intracranial PFS (iPFS) assessed by BICR | Intracranial PFS (iPFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1 | 48 months | |
Secondary | Extracranial PFS (ePFS) assessed by investigator | Extracranial PFS (ePFS) assessed by investigator using RECIST 1.1 | 48 months | |
Secondary | Extracranial PFS (ePFS) assessed by BICR | Extracranial PFS (ePFS) assessed by Blinded Independent Central Radiological (BICR) using RECIST 1.1 | 48 months | |
Secondary | Objective Response Rate (ORR) assessed by investigator using RECIST 1.1 | Objective Response Rate (ORR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1 | 48 months | |
Secondary | Disease Control Rate (DCR) assessed by investigator using RECIST 1.1 | Disease Control Rate (DCR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1 | 48 months | |
Secondary | Duration of Response (DoR) assessed by investigator using RECIST 1.1 | Duration of Response (DoR) for Intracranial lesions and Extracranial lesions assessed separately by investigator using RECIST 1.1 | 48 months | |
Secondary | Overall ORR assessed by investigator using RECIST 1.1 | Overall ORR assessed by investigator using RECIST 1.1 | 48 months | |
Secondary | Overall DCR assessed by investigator using RECIST 1.1 | Overall DCR assessed by investigator using RECIST 1.1 | 48 months | |
Secondary | Overall DoR assessed by investigator using RECIST 1.1 | Overall DoR assessed by investigator using RECIST 1.1 | 48 months | |
Secondary | ORR for Intracranial lesions assessed by investigator using RANO-BM | ORR for Intracranial lesions assessed by investigator using RANO-BM | 48 months | |
Secondary | DCR for Intracranial lesions assessed by investigator using RANO-BM | DCR for Intracranial lesions assessed by investigator using RANO-BM | 48 months | |
Secondary | DoR for Intracranial lesions assessed by investigator using RANO-BM | DoR for Intracranial lesions assessed by investigator using RANO-BM | 48 months | |
Secondary | Overall Survival | Overall Survival | 48 months | |
Secondary | Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). | 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. | 48 months | |
Secondary | Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BN20 (EORTC QLQ-BN20). | 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. | 48 months | |
Secondary | Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE) | Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE) | 48 months | |
Secondary | Neurological function improvement rate assessed by RANO-BM criteria | Neurological function improvement rate assessed by RANO-BM criteria | 48 months | |
Secondary | Number of participants with treatment-related Adverse Events as assessed by CTCAE v5.0 | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | 48 months | |
Secondary | Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0 | Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0 | 48 months | |
Secondary | Incidence of laboratory abnormalities collected by hematology tests during the study 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 | |
Secondary | Incidence of laboratory abnormalities collected by biochemistry tests during the study 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 | |
Secondary | Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0 | Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0 | 48 months | |
Secondary | Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period. | Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period. | 48 months | |
Secondary | Systolic and Diastolic Blood Pressure assessed during the study period. | Systolic and Diastolic Blood Pressure assessed during the study period. | 48 months | |
Secondary | Pulse rate assessed during the study period. | Pulse rate to assessed during the study period. | 48 months | |
Secondary | Body temperature assessed during the study period. | Body temperature assessed during the study period. | 48 months | |
Secondary | PFS assess by BICR | Blinded Independent Central Radiological (BICR) assessment of PFS using modified RECIST 1.1. | 48 months |
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