EGFR-mutated non-small cell lung cancer (NSCLC) not amenable for curative treatment intention and candidates for EGFR-inhibitor in first line.
Conditions
Interventions
Trade Name: VIZIMPRO
Pharmaceutical Form: Tablet
INN or Proposed INN: Osimertinib
Other descriptive name: OSIMERTINIB
Trade Name: GIOTRIF
Pharmaceutical Form: Tablet
INN or Proposed INN: Afatinib
CAS
Sponsors
Region Skåne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the study, subjects must meet the following criteria: • The subject has given written consent to participate in the study. • Histological or cytological diagnosis of NSCLC. • Clinical stage III/IV disease or a recurrence not amenable for curative treatment intention. • Measurable disease according to RECIST 1.1 criteria or equivalent/modified criteria. • Any WHO PS. • Age 18 years or older, no upper age limit. • EGFR-mutation in tumor (in cases where tumor tissue is not available for mutation analysis, circulating tumour-DNA (ctDNA) in plasma may serve as inclusion criteria). • Treatment-naive with regard to TKI’s • Negative pregnancy test (blood or urine test) • For fertile participants, adequate contraception should be used; intrauterine device, bilateral tubal occlusion, vasectomy or abstinence (a reduced effect of hormonal contraception methods due to the drugs cannot be excluded). Pregnancy should be avoided during treatment and the first 4 months following treatment discontinuation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: Subjects must not be included in the study if any of the following criteria are met: • Condition incompatible with the study or with the planned treatment. • Present second primary malignancy with metastatic potential. • Intake of hypericum perforatum. • All subjects should avoid concomitant use of medications with known interaction with planned treatment, whenever feasible. If the administration of a medication interacts with any of the three investigational treatments and cannot be exchanged or managed in order to avoid interactions the patient is excluded from the trial. o Drugs that can either increase or decrease the concentration of osimertinib in plasma: ? Strong activators of CYP3A. Simultaneous administration should be avoided. ? Regular CYP3A4-inhibitors should be used with caution or be avoided. o Drugs that can either increase or decrease the concentration of afatinib in plasma: ? Strong inhibitors of P-glycoprotein should not be administered simultaneously with afatinib, instead it should preferably be 6-12 hours between. ? Strong activators of P-glycoprotein may reduce exposure of afatinib o Drugs that can either increase or decrease the concentration of dacomitinib in plasma: ? Proton pump inhibitors should be avoided. ? Simultaneous administration of drugs that are metabolized by CYP2D6 should be avoided. If simultaneous use of that kind of medications are considered necessary, dose recommendations for simultaneous use of respective drug should be followed. • Any evidence of severe or uncontrolled systemic diseases which in the investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardise compliance with the protocol. Screening for chronic conditions is not required. • Gastrointestinal conditions incompatible with swallowing or precluding absorption of the study drug. • Pregnancy or refusal to use contraceptives. • Abnormal findings of blood chemistry not compatible with the study drug according to investigator. • History of hypersensitivity to the study drug (or drugs with a similar chemical structure or class) or any excipients. • Severe hepatic impairment/renal function incompatible with study drug according to investigator. • Hereditary conditions with galactose intolerance, total lactase deficiency or glucose -galactose malabsorption • Congenital long QT syndrome • Judgment by the investigator that the subject should not participate in the study, e.g., if the subject is unlikely to comply with study procedures, restrictions and requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of ERIS is to identify clinically relevant molecular profiles and biomarkers in blood and tumor for treatment decisions and management of resistance mechanisms.;Secondary Objective: The secondary objectives of ERIS are to evaluate the optimal sequence of EGFR-inhibitors, tumor response, adverse effects, and life quality of the study participants. ;Primary end point(s): The primary endpoint is to identify biomarkers for response, primary and acquired resistance and toxicity through data analysis and bioinformatics of molecular profiling of tumor and consecutive blood samples. Biomarker studies in ERIS will include: 1)Tumor-derived cell-free DNA, i.e. ctDNA, will be analyzed in plasma (and in some cases other fluids, e.g. pleural effusion) to search for potential resistance mechanisms to EGFR-TKIs, to identify early progression and to monitor treatment response. The sensitizing EGFR-mutation, EGFR T790M that confer EGFR-TKI resistance and possibly other tumor mutations, or genetic alterations will be analyzed, either alterations detected in pre-treatment tumor tissue or alterations being screened for in liquid biopsies. This study will be conducted in real-time as tissue, cytology and blood samples are assembled in ERIS. 2)Proximity Extension Analysis (PEA) protein profiling and RNA expression analysis will be performed on tumor tissue. Obtained markers will subsequently be analyzed with exploratory bioinformatics to set up signaling networks possible to follow longitudinally during the disease course. Furthermore, biomarker candidates may be validated as potential drug candidates. 3)Bypass signaling is one reason of TKI-resistance. On tumor biopsies prior treatment, bypass signaling mechanisms with focus on Eph signaling components will be analyzed in situ. Upon relapse, the same reactions will be carried out on re-biopsies and differences will be evaluated in the context of response to EGFR-TKI. 4)Exosomes isolated from p | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: 1) Time to treatment failure (TTF) of EGFR-inhibitor sequence (total time on TKI) 2) Progression-free survival (PFS) in each treatment line 3) Overall survival (OS) 4) Objective response rate (ORR) in first line and the entire sequence of treatment with EGFR-inhibitors 5) Disease control rate in (DCR) first line and the entire sequence of treatment with EGFR-inhibitors 6) Adverse events (AE) 7) Quality of life (QoL) as assessed through Lung Cancer Symptom Scale (LCSS) ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated a few years into the study and when the study is completed. | — |
Countries
Sweden
Contacts
Public ContactSkåne
Region
Outcome results
None listed