Uncommon EGFR AZD9291
Ключови думи
Резюме
Описание
This is a single-arm phase II trial to evaluate the efficacy of AZD9291 (experimental) NSCLC patients with uncommon EGFR mutation. The primary endpoint of the study is objective response rate. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9).
In this study, we expect an objective response rate of about 30% for the experimental arm (AZD9291 therapy) compared to that of about 10% in the historical control based on previous studies. A sample size of 33 efficacy-evaluable patients would provide a power of 90% for testing the null hypothesis of 10% ORR vs. alternative hypothesis of 30% using a single-arm exact binomial test with a 1=sided significance level of 5%. The experimental therapy will be rejected if 6 or fewer patients out of 33 respond. Allowing for a follow-up loss rate of 10%, the total sample size is 37 patients.
Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Subjects (with the exception of subjects with insulin dependent diabetes) must fast for ≥1 hours prior to taking a dose to ≥2 hour post dose. Water is permitted during this fasting period. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation. If the efficacy will be proven, the patient could receive the treatment continuously.
Дати
| Последна проверка: | 01/31/2018 |
| Първо изпратено: | 01/08/2018 |
| Очаквано записване подадено: | 02/04/2018 |
| Първо публикувано: | 02/06/2018 |
| Изпратена последна актуализация: | 02/04/2018 |
| Последна актуализация публикувана: | 02/06/2018 |
| Действителна начална дата на проучването: | 12/31/2015 |
| Приблизителна дата на първично завършване: | 12/30/2017 |
| Очаквана дата на завършване на проучването: | 07/30/2019 |
Състояние или заболяване
Интервенция / лечение
Drug: AZD9291
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Experimental: AZD9291 Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). | Drug: AZD9291 Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 19 Years Да се 19 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: - Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20 - metastatic or recurrent NSCLC - Be 19years of age on day of signing informed consent - ECOG performance status of 0 to 2 - At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.) - Untreated asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery - At least 2 weeks later after whole brain radiotherapy or at least 4 weeks later after palliative thoracic radiotherapy - Adequate organ function as evidenced by the following; Absolute neutrophil count > 1.5 x 109/L; Hb > 9.0g/dL; platelets > 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT < 2.5 ULN if no demonstrable liver metastases or < 5 UNL in the presence of liver metastases, CCr ≥ 50mL/min - Written informed consent form Exclusion Criteria: - Prior treatment with EGFR TKI - Major surgery undertaken less than 4 weeks before the study - Localized palliative radiotherapy unless completed more than 2 weeks before the study - Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia - Pregnant or nursing women (Women of reproductive potential have to agree to use an adequate contraceptive method) - Uncontrolled symptomatic brain metastasis - Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or well-treated thyroid cancer - Concomitant use of CYP3A4 inducers/inhibitors - Prolonged QT interval in ECG (QTc >450 msec) - Prior history of interstitial lung disease |
Резултат
Първични изходни мерки
1. Objective response rate [through study completion, an average of 2 years]
