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Report for Clinical Trial NCT03257124

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT03257124 Non-Small Cell Lung Cancer With EGFR T790M Mutation With Brain and/or Leptomeningeal Metastasis Failed Tyrosine Kinase Inhibitors
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Meningeal Carcinomatosis
HPO:Neoplasm of the lung Non-small cell lung carcinoma

1 Interventions

Name: AZD9291

Description: AZD9291 160mg per oral daily (1 cycle of 28 days)
Type: Drug
Group Labels: 1

AZD9291 in BM or LM cohort in T790M positive


Primary Outcomes

Description: 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

Measure: Overall response rate (ORR) in CNS -brain metastasis cohort

Time: December, 2019 (one-year follow-up from last patient -in)

Description: From the date of study start to the date of all cause death

Measure: Overall survival - Leptomeningeal with or without brain metastasis cohort

Time: 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

Secondary Outcomes

Description: 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.

Measure: Whole body disease control rate (DCR)

Time: December, 2019 (one-year follow-up from last patient -in)

Description: Time to brain progression is measured from the date of start of study to the date of progression of BM or LM.

Measure: Time to brain progression

Time: December, 2019 (one-year follow-up from last patient -in)

Description: measured from the date of start of study to the date of disease progression or death from any cause.

Measure: Progression free survival (PFS) in BM cohort

Time: December, 2019 (one-year follow-up from last patient -in)

Description: OS is measured from the date of start of study to the date of death from any cause

Measure: Overall survival (OS)

Time: December, 2019 (one-year follow-up from last patient -in)

Description: Adverse events will be measured by the CTCAE scale, version 4.

Measure: Adverse events (AEs)

Time: December, 2019 (one-year follow-up from last patient -in)

Description: Exploratory analysis of EGFR mutation/T790M in tissue, plasma or cerebrospinal fluid (CSF)

Measure: Exploratory analysis of EGFR mutation/T790M

Time: December, 2019 (one-year follow-up from last patient -in)

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 T790M

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. --- T790M ---

Study of AZD9291 in NSCLC Patients Harboring T790M Mutation Who Failed EGFR TKI and With Brain and/or LMS AZD9291 is an oral potent irreversible EGFR TKI selective for sensitizing EGFR mutation and T790M resistance mutation but sparing wild-type EGFR. --- T790M ---

Study of AZD9291 in NSCLC Patients Harboring T790M Mutation Who Failed EGFR TKI and With Brain and/or LMS AZD9291 is an oral potent irreversible EGFR TKI selective for sensitizing EGFR mutation and T790M resistance mutation but sparing wild-type EGFR. --- T790M --- --- T790M ---

Further, previous studies with AZD9291 showed anecdotal case series or undetermined for T790M mutation status, indicating more systematic study is warranted. --- T790M ---

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. --- T790M ---

Adverse events will be measured by the CTCAE scale, version 4.. Exploratory analysis of EGFR mutation/T790M. --- T790M ---

Exploratory analysis of EGFR mutation/T790M in tissue, plasma or cerebrospinal fluid (CSF). --- T790M ---

Inclusion Criteria: - EGFR activating mutant NSCLC patients who failed EGFR TKIs (gefitinib, erlotinib, or afatinib) and develop CNS disease (BM and/or LM) with T790M mutation either tissue or plasma. --- T790M ---

- Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment - History of hypersensitivity to AZD9291 - Known intracranial haemorrahge which is unrelated to tumor Refractory nausea and vomiting Inclusion Criteria: - EGFR activating mutant NSCLC patients who failed EGFR TKIs (gefitinib, erlotinib, or afatinib) and develop CNS disease (BM and/or LM) with T790M mutation either tissue or plasma. --- T790M ---

- Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment - History of hypersensitivity to AZD9291 - Known intracranial haemorrahge which is unrelated to tumor Refractory nausea and vomiting Non-Small Cell Lung Cancer With EGFR T790M Mutation With Brain and/or Leptomeningeal Metastasis Failed Tyrosine Kinase Inhibitors Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Meningeal Carcinomatosis 1. --- T790M ---

Primary end points - Overall response rate (ORR) in CNS -brain metastasis cohort - Overall survival - Leptomeningeal with or without brain metastasis cohort 2. Secondary end points - Whole body disease control rate (DCR) - Time to brain progression - Progression free survival (PFS) in BM cohort - Overall survival (OS) - Adverse events (AEs) - Exploratory analysis of EGFR mutation/T790M in tissue, plasma or cerebrospinal fluid (CSF) 3. Treatment AZD9291 160mg po daily (1 cycle of 28 days) 4. Total patient sample size Eligible patients will be divided into two cohorts, brain metastasis (BM) cohort and leptomeningeal metastasis (LM) with or without BM cohort. --- T790M ---



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