EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer Clinical Trial
— ELIOSOfficial title:
A Multicentre, Open-label, Single-arm, Molecular Profiling Study of Patients With EGFR Mutation-positive Locally Advanced or Metastatic NSCLC Treated With Osimertinib
| Verified date | October 2023 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.
| Status | Completed |
| Enrollment | 156 |
| Est. completion date | September 19, 2023 |
| Est. primary completion date | September 19, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 130 Years |
| Eligibility | Inclusion Criteria: 1. Provision of informed consent prior 2. Patients aged 18 years or older 3. Patients with histological confirmation of locally advanced or metastatic NSCLC 4. Patients with M1 stage according to the Tumor, Node and Metastasis Classification of Malignant Tumours (TNM) 5. Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be associated with EGFR TKI sensitivity 6. Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). 7. Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumour or metastatic tumour tissue 8. WHO performance status 0-1 9. Life expectancy =12 weeks 10. Capacity to swallow 11. Patients able to complete study and within geographical proximity allowing for adequate follow up 12. Resolution of all acute toxic effects of previous anticancer therapy 13. Female patients must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential 14. Male patients must be willing to use barrier contraception Exclusion Criteria: 1. Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy 2. Patients diagnosed with another lung cancer subtype 3. Patients with an EGFR exon 20 insertion 4. Patients with just one measurable or evaluable tumour lesion that has been resected or irradiated prior to their enrolment in the study 5. Second active neoplasia 6. Treatment with an investigational drug within five half-lives of the compound 7. Participation in another clinical study with an investigational product (IP) during the last 3 weeks before the first day of study treatment 8. Patients who have received prior immunotherapies 9. Patients who have received prior EGFR treatments for lung cancer 10. Patients who have received prior treatment with an EGFR TKI including in the adjuvant setting 11. Patients who have received previous treatment for metastatic or stage IV disease 12. Prior treatment with cytotoxic chemotherapy for advanced NSCLC 13. Patients with a history of cancer that has been completely treated, with no evidence of malignant disease currently cannot be enrolled in the study if their chemotherapy was completed less than 6 months prior and/or have received a bone marrow transplant less than 2 years before the first day of study treatment 14. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy 15. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or active infection (eg, patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled Hepatitis B virus (HBV) infection. 16. Patients who have had a surgical procedure unrelated to the study within 14 days or major surgery within 1 month prior to the administration of the study drug 17. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis 18. Any of the following cardiac criteria: Mean resting QT interval corrected for heart rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, hypomagnesaemia, hypocalcaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval 19. Spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. 20.Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib 21.Inadequate bone marrow reserve or organ function 22.Female patients who are breastfeeding 23.Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome (CYP) 3A4. 24.Patient unwilling to undergo a biopsy at the time of disease progression 25.History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib 26.Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements 27.Involvement in the planning and/or conduct of the study 28.Previous enrolment in the present study |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Research Site | Brescia | |
| Italy | Research Site | Meldola | |
| Italy | Research Site | Monza | |
| Italy | Research Site | Parma | |
| Italy | Research Site | Roma | |
| Italy | Research Site | Terni | |
| Korea, Republic of | Research Site | Busan | |
| Korea, Republic of | Research Site | Cheongiu | |
| Korea, Republic of | Research Site | Seongnam | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Korea, Republic of | Research Site | Seoul | |
| Malaysia | Research Site | Johor Bahru | |
| Malaysia | Research Site | Kuantan | |
| Malaysia | Research Site | Kuching | |
| Malaysia | Research Site | Lembah Pantai | |
| Malaysia | Research Site | Pulau Pinang | |
| Spain | Research Site | A Coruña | |
| Spain | Research Site | Barcelona | |
| Spain | Research Site | Las Palmas de Gran Canaria | |
| Spain | Research Site | Madrid | |
| Spain | Research Site | Sevilla | |
| United States | Research Site | Athens | Georgia |
| United States | Research Site | Atlanta | Georgia |
| United States | Research Site | Boston | Massachusetts |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca | Parexel |
United States, Italy, Korea, Republic of, Malaysia, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0 | To summarize the safety and tolerability profile of osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer | At every visit from signing informed consent until 28 days after last dose of study treatment | |
| Primary | Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression as defined by the Investigator | To characterize the frequency of genetic and proteomic markers at disease progression regardless of their prevalence. | Tumour Genetic and Proteomic markers will be assessed from tissue samples collected prior to initiation of treatment and at the time of disease progression for max 4.2 years | |
| Secondary | Progression-free survival (PFS) | PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed RECIST 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression. | At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years | |
| Secondary | Objective Response Rate (ORR) | ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later. | At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years | |
| Secondary | Duration of Response (DoR) | DoR is defined as the time from the date of first documented response, (that is subsequently confirmed) until date of documented progression or death in the absence of disease progression, the end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. | From time of first documented response until date of documented progression or death in the absence of disease progression or end of study up to max 4.2 years | |
| Secondary | Time toTreatment Discontinuation or Death (TTD) | TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death. | At every visit from enrolment to end of treatment or death or end of study for max 4.2 years | |
| Secondary | Time to first subsequent therapy or Death (TFST) | TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death. | At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years | |
| Secondary | Disease Control Rate | Percentage of patients who have a best overall response, complete response, partial response or stable disease. | At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years | |
| Secondary | PFS in patient subgroups defined by molecular profile | PFS will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: Epidermal growth factor receptor (EGFR) Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA). | At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years | |
| Secondary | ORR in patient subgroups defined by molecular profile | ORR will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA. | At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years | |
| Secondary | TTD in patient subgroups defined by molecular profile | TTD will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA. | At every visit from enrolment to start of first subsequent therapy or death or end of study for max 4.2 years | |
| Secondary | Tumour shrinkage/depth of response in patient subgroups defined by molecular profile | Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions. Tumour shrinkage/depth of response will additionally be analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA. | At baseline and every 8 weeks from enrolment until 3.5 years and every 10 weeks until disease progression or death or end of study for max 4.2 years | |
| Secondary | Proportion of patients with pre-specified characteristics will be summarised by molecular profile | The patient characteristics will include: gender (male/female), age (<65yrs/>65yrs), race (Asian/non Asian), and WHO Performance Status (0/1). These will be summarized by subgroups defined by molecular profile, including but not limited to: EGFR Ex 19 del or L858R mutation and EGFR Ex19 del or L858R detectable in plasma derived ctDNA. | At baseline |