Study of AZD9291 in NSCLC Patients Harboring T790M Mutation Who Failed EGFR TKI and With Brain and/or LMS
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03257124|
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : September 7, 2017
AZD9291 is an oral potent irreversible EGFR TKI selective for sensitizing EGFR mutation and T790M resistance mutation but sparing wild-type EGFR. Preclinical studies indicate that AZD9291 has significant exposure in the brain and activity against EGFR mutant brain metastasis. In addition, anti-tumor activities of AZD9291 in patients with advanced stage EGFR mutant NSCLC including patients with brain metastasis have been reported in an ongoing Phase I study. More recently, AZD9291 at a dose of 160mg also showed promising efficacy in heavily pre-treated patients with leptomeningeal disease from EGFR mutant NSCLC. Among 11 evaluable for response, 6 patients had LM imaging improvement and 3 out of 7 patients with abnormal neurological exam at baseline had symptomatic improvement. Compared to AZD9291, other 3rd generation EGFR TKIs, rociletinib or HM61713 has not been reported to be effective in most of CNS disease of NSCLC. Further, previous studies with AZD9291 showed anecdotal case series or undetermined for T790M mutation status, indicating more systematic study is warranted.
Based on these data, the investigators are going to conduct phase II study of AZD9291 in NSCLC patients harboring T790M mutation who failed EGFR TKIs and brain and/or leptomeningeal metastasis.
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer With EGFR T790M Mutation With Brain and/or Leptomeningeal Metastasis Failed Tyrosine Kinase Inhibitors||Drug: AZD9291||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Multicenter, Phase II Study of AZD9291 in Non-small Cell Lung Cancer (NSCLC) Patients Harboring T790M Mutation Who Failed EGFR TKIs and With Brain and/or Leptomeningeal Metastasis|
|Actual Study Start Date :||May 8, 2017|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||December 31, 2019|
Experimental: AZD9291 in BM or LM cohort in T790M positive
AZD9291 160mg per oral daily (1 cycle of 28 days)
- Overall response rate (ORR) in CNS -brain metastasis cohort [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]At least one visit response of CR (complete response) or PR (partial response) that is confirmed at least 4 weeks later by using RECIST 1.1 criteria
- Overall survival - Leptomeningeal with or without brain metastasis cohort [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]From the date of study start to the date of all cause death
- Whole body disease control rate (DCR) [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]At least one visit response of CR (complete response), PR (partial response) or SD (stable disease) that is confirmed at least 4 weeks later by using RECIST 1.1 criteria.
- Time to brain progression [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]Time to brain progression is measured from the date of start of study to the date of progression of BM or LM.
- Progression free survival (PFS) in BM cohort [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]measured from the date of start of study to the date of disease progression or death from any cause.
- Overall survival (OS) [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]OS is measured from the date of start of study to the date of death from any cause
- Adverse events (AEs) [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]Adverse events will be measured by the CTCAE scale, version 4.
- Exploratory analysis of EGFR mutation/T790M [ Time Frame: December, 2019 (one-year follow-up from last patient -in) ]Exploratory analysis of EGFR mutation/T790M in tissue, plasma or cerebrospinal fluid (CSF)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257124
|Contact: Myung-Ju Ahn, Professoremail@example.com|
|Korea, Republic of|
|Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine||Recruiting|
|Seoul, Korea, Republic of, 135-710|
|Contact: Myung-Ju Ahn, M.D. +82-2-3410-3438 firstname.lastname@example.org|