Clinical trial • Phase III • Oncology
OSIMERTINIB for Stage IA2-IA3 non-small cell lung cancer | EGFR-mutant non-small cell lung cancer
Phase III trial of OSIMERTINIB for Stage IA2-IA3 non-small cell lung cancer | EGFR-mutant non-small cell lung cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Stage IA2-IA3 non-small cell lung cancer | EGFR-mutant non-small cell lung cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 09-08-2024
- First CTIS Authorization Date
- 25-09-2024
Trial design
Randomised, osimertinib 80 mg once daily (dose may be reduced to 40 mg once daily at investigator discretion) versus matching placebo once daily (matching placebo if dose reduction to 40 mg).-controlled Phase III trial in Germany, Italy, Poland and others.
- Randomised
- Yes
- Comparator
- Osimertinib 80 mg once daily (dose may be reduced to 40 mg once daily at Investigator discretion) versus matching placebo once daily (matching placebo if dose reduction to 40 mg).
- Target Sample Size
- 361
- Trial Duration For Participant
- 1095
Eligibility
Recruits 361 Vulnerable population is selected. Participants are adult patients (≥18 years). Informed consent is required from each adult participant using the Subject Information Sheet and Adult Subject Informed Consent Form; separate pre-screening ICF, optional genetic research ICF and Pregnant Partner ICF documents are provided. No assent/parental consent procedures (minors are excluded). ICFs are provided in relevant country/language-specific versions (documents available for IT, PL and other local versions)..
- Pregnancy Exclusion
- Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. Male subjects must be willing to use barrier contraception.
- Vulnerable Population
- Vulnerable population is selected. Participants are adult patients (≥18 years). Informed consent is required from each adult participant using the Subject Information Sheet and Adult Subject Informed Consent Form; separate pre-screening ICF, optional genetic research ICF and Pregnant Partner ICF documents are provided. No assent/parental consent procedures (minors are excluded). ICFs are provided in relevant country/language-specific versions (documents available for IT, PL and other local versions).
Inclusion criteria
- {"criterion_text":"- Male or female, at least ≥ 18 years.\n- Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential. Male subjects must be willing to use barrier contraception.\n- NSCLC, of non-squamous histology.\n- Stage IA2 or IA3 disease, based on TNM8 classification.\n- Complete surgical resection (R0) of the primary NSCLC by lobectomy, bilobectomy, segmentectomy or sleeve resection.\n- Complete recovery from surgery at the time of randomisation. Study intervention cannot commence within 4 weeks following surgery. No more than 12 weeks may have elapsed between surgery and randomisation for participants.\n- World Health Organization performance status of 0 or 1.\n- Provision of tumour sample for central pathology assessment of pathologic risk factors and to assess EGFR mutation status prior to randomisation.\n- A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R).\n- Minimum life expectancy of > 6 months."}
Exclusion criteria
- {"criterion_text":"- Mixed small cell and non-small cell cancer history.\n- Major surgery or significant traumatic injury within 4 weeks of the first dose of study intervention.\n- Participants currently receiving medications or herbal supplements known to be strong inducers of CYP3A4.\n- Participants with incomplete (R1/R2) resection, or who have undergone pneumonectomy or only wedge resection.\n- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including HCV and HIV or active uncontrolled HBV infection.\n- History of another primary malignancy, including any known or suspected synchronous primary lung cancer, except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence.\n- Any of the following cardiac criteria: Mean resting QTcF interval > 470 ms, obtained from triplicate ECGs performed at screening / Any abnormalities in rhythm, conduction, or morphology of resting ECG / Any factors that increase the risk of QTcF prolongation or risk of arrhythmic events.\n- History of interstitial lung disease.\n- Inadequate bone marrow reserve or organ function.\n- Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study intervention.\n- Prior treatment with any anticancer therapy for NSCLC (including chemotherapy, radiotherapy, immunotherapy, and EGFR-TKIs)."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Disease free survival (DFS) in the high-risk stratum by investigators' assessment.","definition_or_measurement_approach":"DFS measured by investigators' assessment (disease-free survival assessment performed by investigators in the high-risk stratum)."}
Secondary endpoints
- {"endpoint_text":"- Disease free survival (DFS) in the overall population by investigator's assessment.","definition_or_measurement_approach":"DFS measured by investigator's assessment in the overall population."}
- {"endpoint_text":"- Disease free survival (DFS) in both the high-risk stratum and overall population.","definition_or_measurement_approach":"DFS measured in both the high-risk stratum and the overall population (method: investigator assessment as specified)."}
- {"endpoint_text":"- Overall survival (OS) in participants in both the high-risk stratum and overall population.","definition_or_measurement_approach":"Overall survival assessed in both high-risk stratum and overall population (time to death from any cause)."}
- {"endpoint_text":"- Impact of osimertinib versus placebo on physical functioning in both the high-risk stratum and overall population.","definition_or_measurement_approach":"Assessment of physical functioning (patient-reported / functional scales as defined in protocol) in both strata/population."}
- {"endpoint_text":"- Effectiveness of osimertinib versus placebo by assessment of central nervous system disease free survival (DFS) in both the high-risk stratum and the overall population.","definition_or_measurement_approach":"CNS disease-free survival measured in both the high-risk stratum and overall population (assessment method per protocol imaging/clinical criteria)."}
- {"endpoint_text":"- Characterise the pharmacokinetics of osimertinib and its metabolites (AZ13575104 [AZ5104]) in the overall population.","definition_or_measurement_approach":"Pharmacokinetic characterisation of osimertinib and metabolites (PK sampling and analysis per protocol)."}
- {"endpoint_text":"- Safety and tolerability profile of osimertinib versus placebo in the overall population.","definition_or_measurement_approach":"Safety and tolerability assessed via adverse event reporting, CTCAE grading, laboratory assessments and other safety measures per protocol."}
Recruitment
- Planned Sample Size
- 361
- Recruitment Window Months
- 99
- Consent Approach
- Informed consent is obtained from adult participants (≥18 years) via Subject Information Sheets and Informed Consent Forms. Separate ICFs are provided for pre-screening, pregnant partners and optional genetic research. Consent is provided by the participant; no assent/parental consent provisions (minors excluded). Local/country-specific language ICFs are available (documents for Italy (IT), Poland (PL), Spain and other local versions are included).
Geography
- Total Number Of Sites
- 29
- Total Number Of Participants
- 21
Germany
- Earliest CTIS Part Ii Submission Date
- 01-08-2024
- Latest Decision Or Authorization Date
- 08-01-2026
- Processing Time Days
- 525
- Number Of Sites
- 6
- Number Of Participants
- 1
Sites
- Site Name
- Evangelische Lungenklinik Berlin Krankenhausbetriebs gGmbH
- Department Name
- Klinik fuer Pneumologie
- Contact Person Name
- Christian Grohe
- Contact Person Email
- christian.grohe@jsd.de
- Site Name
- Klinikum Wuerzburg Mitte gGmbH
- Department Name
- Standort Missioklinik
- Contact Person Name
- Jens Kern
- Contact Person Email
- jens.kern@kwm-klinikum.de
- Site Name
- Klinikum Esslingen GmbH
- Department Name
- Klinik fuer Kardiologie und Pneumologie
- Contact Person Name
- Martin Faehling
- Contact Person Email
- m.faehling@klinikum-esslingen.de
- Site Name
- Universitaetsklinikum Schleswig-Holstein AöR
- Department Name
- Studienzentrum Pneumologie – Infektiologie – Onkologie
- Contact Person Name
- Sabine Bohnet
- Contact Person Email
- sabine.bohnet@uksh.de
- Site Name
- Ludwig-Maximilians-Universitaet Muenchen
- Department Name
- Campus Innenstadt Medizinische Klinik V
- Contact Person Name
- Amanda Tufman
- Contact Person Email
- amanda.tufman@med.uni-muenchen.de
- Site Name
- Franziskus Hospital Harderberg
- Department Name
- Zentrum fuer Internistische Onkologie und Haematologie
- Contact Person Name
- Petra Hoffknecht
- Contact Person Email
- petra.hoffknecht@niels-stensen-kliniken.de
Italy
- Earliest CTIS Part Ii Submission Date
- 01-08-2024
- Latest Decision Or Authorization Date
- 08-01-2026
- Processing Time Days
- 525
- Number Of Sites
- 10
- Number Of Participants
- 14
Sites
- Site Name
- Careggi University Hospital
- Department Name
- Oncologia
- Contact Person Name
- Lorenzo Livi
- Contact Person Email
- lorenzo.livi@unifi.it
- Site Name
- Istituto Europeo Di Oncologia S.r.l.
- Department Name
- Oncologia
- Contact Person Name
- Filippo De Marinis
- Contact Person Email
- filippo.demarinis@ieo.it
- Site Name
- Istituto Tumori Bari Giovanni Paolo II
- Department Name
- Oncologia
- Contact Person Name
- Domenico Galetta
- Contact Person Email
- galetta@oncologico.bari.it
- Site Name
- IRCCS Ospedale Policlinico San Martino
- Department Name
- Oncologia
- Contact Person Name
- Carlo Genova
- Contact Person Email
- carlo.genova@hsanmartino.it
- Site Name
- I.F.O. Istituti Fisioterapici Ospitalieri
- Department Name
- Oncologia
- Contact Person Name
- Federico Cappuzzo
- Contact Person Email
- federico.cappuzzo@ifo.it
- Site Name
- ARNAS Garibaldi Di Catania
- Department Name
- Oncologia
- Contact Person Name
- Concetta Sergi
- Contact Person Email
- consergi1974@gmail.com
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Department Name
- Oncologia
- Contact Person Name
- Silvia Novello
- Contact Person Email
- silvia.novello@unito.it
- Site Name
- Azienda Ospedaliera Dei Colli
- Department Name
- Oncologia
- Contact Person Name
- Danilo Rocco
- Contact Person Email
- danilorocc@yahoo.it
- Site Name
- Azienda Ospedaliero Universitaria Parma
- Department Name
- Oncologia
- Contact Person Name
- Marcello Tiseo
- Contact Person Email
- marcello.tiseo@unipr.it
- Site Name
- Istituto Oncologico Veneto
- Department Name
- Oncologia
- Contact Person Name
- Laura Bonanno
- Contact Person Email
- laura.bonanno@iov.veneto.it
Poland
- Earliest CTIS Part Ii Submission Date
- 01-08-2024
- Latest Decision Or Authorization Date
- 08-01-2026
- Processing Time Days
- 525
- Number Of Sites
- 3
- Number Of Participants
- 3
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny Nr 4 W Lublinie
- Department Name
- Katedra i Klinika Chirurgii Klatki Piersiowej
- Contact Person Name
- Marek Sawicki
- Contact Person Email
- marek.sawicki@umlub.pl
- Site Name
- National Institute Of Tuberculosis And Lung Diseases
- Department Name
- Zaklad Genetyki i Immunologii Klinicznej
- Contact Person Name
- Joanna Chorostowska-Wynimko
- Contact Person Email
- j.chorostowska@gmail.com
- Site Name
- Wielkopolskie Centrum Pulmonologii I Torakochirurgii Im. Eugenii I Janusza Zeylandow
- Department Name
- Oddzial Onkologii Klinicznej
- Contact Person Name
- Katarzyna Stencel
- Contact Person Email
- kstencel@wcpit.org
Romania
- Earliest CTIS Part Ii Submission Date
- 01-08-2024
- Latest Decision Or Authorization Date
- 08-01-2026
- Processing Time Days
- 525
- Number Of Sites
- 5
- Number Of Participants
- 1
Sites
- Site Name
- Ovidius Clinical Hospital S.R.L.
- Department Name
- Medical Oncology
- Contact Person Name
- Laura Mazilu
- Contact Person Email
- lauragrigorov@gmail.com
- Site Name
- Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucuresti
- Department Name
- Medical Oncology
- Contact Person Name
- Aurelia Alexandru
- Contact Person Email
- auralexandru@yahoo.com
- Site Name
- Oncolab S.R.L.
- Department Name
- Medical Oncology
- Contact Person Name
- Dan Stelian Stefan Lungulescu
- Contact Person Email
- dan.lungulescu@yahoo.com
- Site Name
- Radiotherapy Center Cluj S.R.L.
- Department Name
- Medical Oncology
- Contact Person Name
- Andrei Ungureanu
- Contact Person Email
- andrei.ungureanu@amethyst-radiotherapy.com
- Site Name
- Spitalul Universitar De Urgenta Bucuresti
- Department Name
- Medical Oncology
- Contact Person Name
- Georgeta Polixenia Iorga
- Contact Person Email
- polixeniaiorga@yahoo.com
Spain
- Earliest CTIS Part Ii Submission Date
- 01-08-2024
- Latest Decision Or Authorization Date
- 08-01-2026
- Processing Time Days
- 525
- Number Of Sites
- 5
- Number Of Participants
- 2
Sites
- Site Name
- Hospital De La Santa Creu I Sant Pau
- Department Name
- Oncologia
- Contact Person Name
- Margarita Majem
- Contact Person Email
- mmajem@santpau.cat
- Site Name
- Hospital Clinico Universitario Lozano Blesa
- Department Name
- Oncologia
- Contact Person Name
- Maria Dolores Isla
- Contact Person Email
- lola.isla@gmail.com
- Site Name
- Hospital Universitario Regional De Malaga
- Department Name
- Oncologia
- Contact Person Name
- Manuel Cobo
- Contact Person Email
- manuelcobodols@yahoo.es
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Oncologia
- Contact Person Name
- Maria Amelia Insa
- Contact Person Email
- ameliainsamolla@gmail.com
- Site Name
- Hospital Alvaro Cunqueiro
- Department Name
- Oncologia
- Contact Person Name
- Martin Emilio Lazaro Quintela
- Contact Person Email
- martin.lazaro.quintela@sergas.es
Sponsor
Primary sponsor
- Full Name
- AstraZeneca AB
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Sweden
Investigational products
- Investigational Product Name
- TAGRISSO 80 mg film-coated tablets
- Active Substance
- OSIMERTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Marketing authorisation present (EU/1/16/1086/004)
- Starting Dose
- 80 mg once daily
- Dose Levels
- 80 mg (can be reduced to 40 mg if required)
- Frequency
- Once daily
- Maximum Dose
- 80 mg daily
- Investigational Product Name
- TAGRISSO 40 mg film-coated tablets
- Active Substance
- OSIMERTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- Oral
- Authorisation Status
- Marketing authorisation present (EU/1/16/1086/003)
- Starting Dose
- 40 mg (used as dose reduction from 80 mg)
- Dose Levels
- 40 mg (dose reduction level)
- Frequency
- Once daily
- Maximum Dose
- 80 mg daily
- Investigational Product Name
- Placebo
- Modality
- Other
- Starting Dose
- Matching placebo once daily
- Frequency
- Once daily (matching active dosing schedule)
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