Study of Osimertinib in Patients With a Lung Cancer With Brain or Leptomeningeal Metastases With EGFR Mutation (ORBITAL)
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|ClinicalTrials.gov Identifier: NCT04233021|
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : February 10, 2020
Treatment of non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutation is mainly based on tyrosine kinase inhibitors (TKIs) targeting EGFR. 1st or 2nd generation inhibitors have been shown to be superior to chemotherapy in terms of Progression-Free Survival (PFS) when used as 1st line treatment.
In case of progression at several metastatic sites, systemic treatment will be considered and will depend on the presence of the TKI resistance mutation, the T790M mutation. In the presence of the T790M mutation, osimertinib is superior to chemotherapy in terms of progression-free survival, while in the absence of the T790M mutation, platinum salt chemotherapy is recommended. In case of local progression, treatment of the site in progression by radiotherapy and/or surgery is considered. As these local treatments can cause long-term adverse effects, systemic treatments are increasingly being considered in this indication.
Brain and leptomeningeal metastases are the most frequent isolated site of progression in EGFR mutated patients treated with TKI. The high frequency of isolated cerebral and leptomeningeal progression is a consequence of the lower diffusion of 1st and 2nd generation TKIs in the central nervous system (CNS). Osimertinib is a 3rd generation TKI that has the particularity of overcoming the T790M mutation and having greater brain penetration than 1st or 2nd generation TKIs, which could make it an attractive therapeutic option in the event of brain progression or leptomeningeal progression. However, its efficacy in patients with cerebral or leptomeningeal metastases is still poorly understood.
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer Metastatic Leptomeningeal Metastasis Brain Metastases EGFR Activating Mutation||Drug: Osimertinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||113 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Multi-centre Study, to Evaluate the Efficacy and Safety of Osimertinib Treatment for Patients With EGFR-mutated Non-small Cell Lung Cancer (NSCLC) With Brain or Leptomeningeal Metastases|
|Estimated Study Start Date :||February 2020|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||July 2022|
Osimertinib 80 mg/d
Osimertinib 80 mg/d
- Objective Response Rate [ Time Frame: 6 months ]Objective Response Rate at 6 months using EANO-ESMO criteria (cohort 1) and RECIST1.1 criteria (cohorts 2, 3, 4)
- Overall Survival [ Time Frame: About 24 months ]Time from enrollment until death due to any cause
- Progression-free survival [ Time Frame: About 24 months ]Time from enrollment to first observation of progression (EANO-ESMO criteria (cohort 1) and RECIST1.1 criteria (cohorts 2, 3, 4)) or date of death (from any cause)
- Incidence, type and severity of adverse event [ Time Frame: From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months) ]Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- Evaluate the Quality of life [ Time Frame: From time of randomisation through treatment period (about 24 months) ]EORTC QLQ-C30-LC13 (Qualify of Life Questionnaire C30 and Lung Cancer 13) questionnaire
- Evaluate the Quality of life [ Time Frame: From time of randomisation through treatment period (about 24 months) ]QLQ BN20 (Brain Neoplasm N20) questionnaire
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): NCT04233021