Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non-small Cell Lung Cancer
Conditions
Brief summary
To assess the efficacy and safety of Alflutinib Mesylate versus Gefitinib in patients with locally advanced or Metastatic Non Small Cell Lung Cancer
Detailed description
This is a Phase III, double-blind, randomised study assessing the efficacy and safety of Alflutinib Mesylate (AST2818) (80 mg orally, once daily) versus Gefitinib (250 mg orally, once daily\] in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive for first-line treatment with an EGFR-TKI.
Interventions
DRUGAlflutinib Mesylate (AST2818) 80mg//40 mg+ placebo
The initial dose of AST2818 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
DRUGGefitinib 250 mg
The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
DRUGPlacebo AST2818 80mg//40 mg
The initial dose of Placebo AST2818 80 mg once daily can be reduced to Placebo AST2818 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Sponsors
Allist Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must meet all the following criteria to be enrolled in this study: subjects will voluntarily participate and sign a written informed consent. 2. Male or female, aged at least 18 years. 3. ECOG performance status of 0 to 2. Life expectancy of at least 12 weeks. 4. Patients had histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma not amenable to curative surgery or radiotherapy. 5. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R). 6. Tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status. 7. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) if the disease has no progression during one year. 8. At least one measurable lesion by CT or MRI. The measureable lesion should receive no local treatments (i.e., radiotherapy) or not used for screening biopsies (If there is only one target lesion that must be biopsied, baseline tumor evaluation is required at least 14 days after screening biopsy) and can be accurately measured at baseline with the longest diameter greater than 10 mm at baseline (if it is a lymph node, short diameter greater than 15 mm is required). If the lesions located at the regions which were previously treated are confirmed to progress, they can be chosen as lesion according to RECIST Version 1.1 9. Females who have fertility potential before menopause should have a pregnancy test in the time period of 7 days prior to start of dosing, should not be breast feeding and must have a negative pregnancy test (blood test or urinalysis) prior to start of dosing; Males and females of child-bearing age must take adequate contraceptive measures within 3 months after signing the informed consent of the study to the last drug treatment.
Exclusion criteria
1. Treatment with any of the following: * Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC, such as standard chemotherapy, targeted therapy, biological therapy, immune therapy and for the prior adjuvant / neo-adjuvant therapy listed in the inclusion criteria VII * Patients received other systemic anticancer therapies for advanced/metastatic non-small cell lung cancer * Patients who have received intrapleural perfusion therapy should be admitted to the group unless the stabilization of hydrothorax is longer than 28 days * Prior treatment with an EGFR-TKI * Major surgery within 4 weeks of the first dose of study drug * Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug and local radiotherapy or palliative radiotherapy for bone metastasis within 14 days before first drug administration * Patients receiving medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 within 7 days before first drug administration and patients continuously taking these medications during investigating period * Patients taking traditional Chinese medicine and preparations whose therapeutic goal is anti-tumors within 7 days before first drug administration; or continuously taking these medications during investigating period * Patients with any factors that increase the risk of QTc prolongation or risk of Torsade ventricular tachycardia event who continuously take these medications during investigating period. * Before the first administration, the duration of discontinuation of other clinical experimental drugs was less than 14 days 2. Unrecovered toxic reaction due to anti-tumor therapy existed, with over 1 grade of CTCAE (except alopecia) or 2 grade if ever applied DDP curing related neuropathy; Bone marrow, liver and kidney organ function please refer to
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) (Months) | At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression ( (approximately 12 months) | Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent alflutinib compared with SoC EGFR-TKI therapy as measured by PFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) evaluated by investigator | At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months) | Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent alflutinib compared with SoC EGFR-TKI therapy as measured by PFS. |
| Objective Response Rate (ORR) | At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months) | ORR was defined as the number (%) of patients with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of alflutinib compared with SoC EGFR-TKI therapy |
| Duration of Response (DoR) | At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months) | Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of alflutinib compared with SoC EGFR-TKI therapy. |
| Overall Survival (OS)- Number of Participants With an Event | From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months) | Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of alflutinib compared with SoC EGFR-TKI therapy |
| Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Questionnaires completed at week 1, 4, 7, 9, 12, 15 , 18,21,27,33,39,45and51 | The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain \[pain in chest, pain in arm or shoulder, and pain in other parts); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. Except for a multi-item scale for dyspnoea, all were single items. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and better function. Higher scores on the symptoms scales indicated greater symptom burden. The results of the analyses were presented in terms of a least squares mean together with its associated 95% profile likelihood CI |
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items | Questionnaires completed at week 1, 4, 7, 9, 12, 15 , 18,21,27,33,39,45and51 | he EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, which were combined to produce 5 functional scales (Physical, Role, Cognitive, Emotional, Social); 3 symptom scales (Fatigue, Pain, Nausea/Vomiting); 6 individual items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties); and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The results of the analyses were presented in terms of a least squares mean together with its associated 95% profile likelihood CI. |
| Depth of Response | At baseline and every 6 weeks for the first 17 months and then every 12 weeks relative to randomisation until progression (approximately 12 months) | The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of alflutinib compared with SoC EGFR-TKI therapy |
Countries
China
Outcome results
None listed