Intracranial Activity of AZD9291 (TAGRISSO) in Advanced EGFRm NSCLC Patients With Asymptomatic Brain Metastases
- Registration Number
- NCT02736513
- Lead Sponsor
- Soroka University Medical Center
- Brief Summary
Patients will receive AZD9291 at a dose of 80 mg once daily. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT (Positron Emission Tomography-Computed Tomography) scan.
In case of isolated CNS progression which may or may not be accompanied by asymptomatic systemic progression, AZD9291 dose will be escalated to 160 mg once daily. For patients whose intracranial disease will progress further, brain radiotherapy (in the form of SRS or WBRT) will be administered; treatment with AZD9291 will be interrupted and re-initiated at a standard dose after the end of radiotherapy course in the absence of symptomatic systemic progression. The treatment will be continued until symptomatic systemic progression, unacceptable toxicity or further intracranial progression following brain radiotherapy administration (whichever occurs first). All patients will be followed until death or 5 years.
- Detailed Description
Patients will receive AZD9291 at a dose of 80 mg once daily. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT scan. In case of isolated CNS progression which may or may not be accompanied by asymptomatic systemic progression, and having in mind the blood-brain-barrier as a possible pharmacokinetic resistance mechanism here, AZD9291 dose will be escalated to 160 mg once daily. For patients whose intracranial disease will progress further, brain radiotherapy (in the form of SRS or WBRT) will be administered; treatment with AZD9291 will be interrupted and re-initiated at a standard dose after the end of radiotherapy course in the absence of symptomatic systemic progression. The treatment will be continued until symptomatic systemic progression, unacceptable toxicity or further intracranial progression following brain radiotherapy administration (whichever occurs first). All patients will be followed until death or 5 years.
Intracranial outcomes will be assessed by modified RECIST criteria (mRECIST) and analyzed. The added value of the increased dose (160 mg) after failure of the standard dose will be assessed as well. Since only neurologically asymptomatic patients are planned to be enrolled, it is important to use mRECIST criteria which allows small brain lesions to be assessed (according to these criteria, ≥ 5mm tumors are considered measurable and up to 5 target lesions are allowed) 1. Systemic response assessment will be done using RECIST 1.1. Exploratory analysis of the outcomes will be performed according to the treatment setting ( treatment-naïve vs. acquired resistance setting) and EGFR mutation subtype. Additionally, serum protein biomarker analysis will be performed in correlation with intracranial and systemic response. Safety parameters will be monitored.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AZD9291 80 mg - previously treated T790M was diagnosed AZD9291 Patients previously treated with first and second generation EFGR TKIs (either Gefitinib, Erlotinib or Afatinib) in whom T790Mwas diagnosed either in the tumor specimen or in the ctDNA after testing it following the most recent disease progression, will be treated with AZD9291 80 mg/day AZD9291 80 mg - naive patients AZD9291 naive patients with tumors harbouring either exon 19 deletion, L858R, T790M, or uncommon sensitizing EGFR mutations, will be treated with AZD9291 80 mg/day AZD9291 80 mg - previously treated unrelated to T790M AZD9291 patients advanced NSCLC previously treated with 1st/2nd generation EGFR TKIs (either gefitinib. erlotinib or afatinib) who progressed unrelated to T790M (T790M-). No restriction regarding the number of prior EGFR TKIs or cytotoxic chemotherapy lines of treatment is applied.
- Primary Outcome Measures
Name Time Method Intracranial overall response rate as defined by modified RECIST 5 years Patients will receive TAGRISSO. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT scan.
- Secondary Outcome Measures
Name Time Method median time to intracranial response (mTTIR) as defined by mRECIST 5 years Patients will receive TAGRISSO. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT scan.
Intracranial disease control rate (IDCR) as defined by mRECIST 5 years Patients will receive TAGRISSO. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT scan.
median intracranial progression free survival (mIPFS) as defined by mRECIST 5 years Patients will receive TAGRISSO. Intracranial response will be assessed with brain MRI scan, systemic evaluation will be done by PET-CT scan.
Trial Locations
- Locations (1)
Shaare Zedek
🇮🇱Jerusalem, Israel