Clinical trial • Phase III • Oncology

OSIMERTINIB for Non-small cell lung cancer (stage IB-IIIA) with EGFR sensitising mutations (Ex19del, L858R)

Phase III trial of OSIMERTINIB for Non-small cell lung cancer (stage IB-IIIA) with EGFR sensitising mutations (Ex19del, L858R).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-small cell lung cancer (stage IB-IIIA) with EGFR sensitising mutations (Ex19del, L858R)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
07-05-2024
First CTIS Authorization Date
20-06-2024

Trial design

Randomised, placebo once daily (arm b) vs osimertinib 80 mg once daily (arm a)-controlled Phase III trial across 37 sites in Belgium, Sweden, Germany and others.

Randomised
Yes
Comparator
Placebo once daily (Arm B) vs osimertinib 80 mg once daily (Arm A)
Target Sample Size
429

Eligibility

Recruits 429 Vulnerable population selected (isVulnerablePopulationSelected = true). Informed consent handled using Subject Information and Informed Consent Forms (adult ICFs) and related addenda; ICF documents available for adult participants and for pregnant partner information. No paediatric/assent forms are provided in the record..

Pregnancy Exclusion
Female patients should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-child-bearing potential.
Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Informed consent handled using Subject Information and Informed Consent Forms (adult ICFs) and related addenda; ICF documents available for adult participants and for pregnant partner information. No paediatric/assent forms are provided in the record.

Inclusion criteria

  • {"criterion_text":"- Male or female, aged at least 18 years.\n- Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology.\n- MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care.\n- Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of pathologic criteria.\n- Confirmation by the central laboratory that the tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M.\n- Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour.\n- Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization.\n- World Health Organization Performance Status of 0 to 1.\n- Female patients should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-child-bearing potential."}

Exclusion criteria

  • {"criterion_text":"- Treatment with any of the following: - Pre-operative or post-operative or planned radiation therapy for the current lung cancer - Pre-operative (neo-adjuvant) platinum based or other chemotherapy - Any prior anticancer therapy - Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time - Major surgery (including primary tumour surgery, excluding placement of vascular access within 4 weeks of the first dose of study drug - Patients currently receiving medications or herbal supplements known to be potent inducers of CYP3A4 - Treatment with an investigational drug within five half-lives of the compound or any of its related material.\n- Patients who have had only segmentectomies or wedge resections.\n- History of other malignancies, except: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of treatment.\n- 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.\n- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).\n- 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.\n- Any of the following cardiac criteria: - Mean resting corrected QT interval (QTc) >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. - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.\n- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.\n- Inadequate bone marrow reserve or organ-function."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Disease free survival (DFS) using investigator assessments.","definition_or_measurement_approach":"DFS measured using investigator assessments (disease free survival as primary efficacy measure)."}

Secondary endpoints

  • {"endpoint_text":"- Assessment of Disease free survival (DFS) rate at 2 years, 3 years, 4 years and 5 years.","definition_or_measurement_approach":"DFS rate assessed at 2, 3, 4 and 5 years (time-point incidence of DFS)."}
  • {"endpoint_text":"- Analysis of Overall Survival (OS)","definition_or_measurement_approach":"Overall survival analysis (time-to-event analysis of death from any cause)."}
  • {"endpoint_text":"- Assessment of Overall Survival (OS) rate at 2 years, 3 years, 4 years and 5 years.","definition_or_measurement_approach":"OS rate assessed at 2, 3, 4 and 5 years (time-point incidence of OS)."}
  • {"endpoint_text":"- Assessing of patient health-related quality of life and symptoms (HRQoL) using SF-36 questionnaire (version 2, standard)","definition_or_measurement_approach":"HRQoL measured using SF-36 questionnaire (version 2)."}
  • {"endpoint_text":"- PK exposure parameters derived from plasma concentrations of Osimertinib and metabolites AZ5104 and AZ7550. Pharmacokinetics data from this study will be analysed using a population PK approach and may also form part of a pooled analysis with other Osimertinib studies; results from these analyses will be reported separately from the CSR.","definition_or_measurement_approach":"PK exposure parameters derived from plasma concentrations of osimertinib and metabolites AZ5104 and AZ7550; analysed using population PK approach; may be pooled with other studies."}
  • {"endpoint_text":"- Safety and tolerability endpoints assessed by number and severity of adverse events, clinical chemistry, haematology, urinalysis, vital signs, physical examination, body weight, digital electrocardiogram (ECG), left Ventricular Ejection Fraction (LVEF), World Health Organization (WHO) Performance Status and Ophthalmologic assessment.","definition_or_measurement_approach":"Safety assessed by incidence and severity of adverse events and laboratory/clinical evaluations (clinical chemistry, haematology, urinalysis, vitals, ECG, LVEF, WHO PS, ophthalmologic assessment)."}

Recruitment

Planned Sample Size
429
Recruitment Window Months
56
Consent Approach
Informed consent obtained from adult participants using Subject Information and Informed Consent Forms. Adult ICFs and related addenda are provided (including Pregnant Partner information and Pre-screening/Withdrawal forms). ICFs available in multiple languages as provided in documents (English, French, Spanish, Italian, German, Dutch, Swedish, Polish). No paediatric assent forms provided.

Geography

Total Number Of Sites
37
Total Number Of Participants
70

Belgium

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
15-04-2025
Processing Time Days
319
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
UZ Brussel
Department Name
Medical Oncology
Contact Person Name
Lore Decoster

Sweden

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
14-04-2025
Processing Time Days
318
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Linkoping University Hospital Region Ostergotland
Department Name
Lungkliniken
Contact Person Name
Anders Vikström

Germany

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
15-04-2025
Processing Time Days
319
Number Of Sites
6
Number Of Participants
7

Sites

Site Name
Klinikum Wuerzburg Mitte gGmbH
Department Name
Innere Medizin
Contact Person Name
Jens Kern
Contact Person Email
jens.kern@missioklinik.de
Site Name
Lungenfachklinik Immenhausen
Department Name
Thoracic Oncology
Contact Person Name
Achim Rittmeyer
Site Name
Kliniken der Stadt Koeln gGmbH
Department Name
Lungenklinik Köln-Merheim
Contact Person Name
Eva Lotte Buchmeier
Contact Person Email
buchmeiere@kliniken-koeln.de
Site Name
LungenClinic Grosshansdorf GmbH
Department Name
Lungenzentrum
Contact Person Name
Martin Reck
Contact Person Email
m.reck@lungenclinic.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
Evangelische Lungenklinik Berlin Krankenhausbetriebs gGmbH
Department Name
Klinik fuer Pneumologie
Contact Person Name
Christian Grohé
Contact Person Email
christian.grohe@pgdiakonie.de

Spain

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
14-04-2025
Processing Time Days
318
Number Of Sites
11
Number Of Participants
20

Sites

Site Name
Hospital Universitario La Paz
Department Name
Carpeño
Contact Person Name
Javier De Castro
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Oncology Service
Contact Person Name
Maria Amelia Insa
Contact Person Email
ameliainsamolla@gmail.com
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncology Service
Contact Person Name
Manuel Domine
Contact Person Email
lungtrialsfjd@gmail.com
Site Name
Hospital Clinico Universitario Lozano Blesa
Department Name
Oncology Service
Contact Person Name
Maria Dolores Isla
Contact Person Email
lola.isla@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology Service
Contact Person Name
Alexandre Martinez
Contact Person Email
alex.martinez@vhebron.net
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Oncology Service
Contact Person Name
Rosa Alvarez
Contact Person Email
rosa.alvarez.al@gmail.com
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Oncology Service
Contact Person Name
Margarita Majem
Contact Person Email
mmajem@santpau.cat
Site Name
Hospital Clinico San Carlos
Department Name
Oncology Service
Contact Person Name
Jose Luis Gonzalez
Contact Person Email
jglarriba@salud.madrid.org
Site Name
Hospital Universitario Regional De Malaga
Department Name
Oncology Service
Contact Person Name
Vanesa Gutierrez
Contact Person Email
vanesa_gutierrez78@hotmail.com
Site Name
Hospital Universitario Donostia
Department Name
Oncology Service
Contact Person Name
Alfredo Paredes
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Oncology Service
Contact Person Name
Mariano Provencio

Italy

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
14-04-2025
Processing Time Days
318
Number Of Sites
10
Number Of Participants
22

Sites

Site Name
Azienda Ospedaliero Universitaria Parma
Department Name
Oncologia Medica
Contact Person Name
Marcello Tiseo
Contact Person Email
marcello.tiseo@unipr.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Oncologia Toracica
Contact Person Name
Angelo Delmonte
Contact Person Email
Angelo.delmonte@irst.emr.it
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia Medica 2
Contact Person Name
Laura Bonanno
Contact Person Email
laura.bonanno@iov.veneto.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
Istituto Europeo Di Oncologia S.r.l.
Department Name
Oncologia Toracica
Contact Person Name
Filippo De Marinis
Contact Person Email
filippo.demarinis@ieo.it
Site Name
Careggi University Hospital
Department Name
Radioterapia Oncologica
Contact Person Name
Lorenzo Livi
Contact Person Email
lorenzo.livi@unifi.it
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Oncologia Medica
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Oncologia Medica
Contact Person Name
Barbara Melotti
Contact Person Email
barbara.melotti@aosp.bo.it
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
Oncologia
Contact Person Name
Gloria Borra
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Department Name
Oncologia
Contact Person Name
Anna Bettini
Contact Person Email
abettini@asst-pg23.it

Poland

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
15-04-2025
Processing Time Days
319
Number Of Sites
5
Number Of Participants
11

Sites

Site Name
Instytut Msf Sp. z o.o.
Contact Person Name
Ewa Kalinka
Contact Person Email
ewakalinka@wp.pl
Site Name
Mazowiecki Szpital Onkologiczny Sp. z o.o.
Department Name
Oddział Onkologii Klinicznej z Pododdziałem Dziennej Chemioterapii
Contact Person Name
Malgorzata Chudzik
Contact Person Email
malgorzata.a.chudzik@gmail.com
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Płuc i Klatki Piersiowej
Contact Person Name
Dariusz Kowalski
Contact Person Email
dariusz.kowalski@coi.pl
Site Name
Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
Department Name
Oddzial III Chorob Pluc z Pododdzialem Onkologicznym
Contact Person Name
Aleksandra Szczesna
Contact Person Email
ola_szczesna@outlook.com
Site Name
Szpital Rejonowy Im. Dr Jozefa Rostka W Raciborzu
Department Name
Dzienny Oddzial Chemioterapii
Contact Person Name
Jerzy Hanslik

France

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
16-04-2025
Processing Time Days
320
Number Of Sites
3
Number Of Participants
7

Sites

Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Service de Pneumologie et Oncologie thoracique
Contact Person Name
Alexis CORTOT
Contact Person Email
alexis.cortot@chru-lille.fr
Site Name
Hopital Tenon
Department Name
Service de Pneumologie
Contact Person Name
Jacques CADRANEL
Contact Person Email
jacques.cadranel@aphp.fr
Site Name
Centre Leon Berard
Department Name
Service d'Oncologie Médicale
Contact Person Name
Maurice Perol

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 USE
Route
oral
Authorisation Status
Authorised (marketing authorisation number EU/1/16/1086/004)
Starting Dose
80 mg
Dose Levels
80 mg
Frequency
once daily
Maximum Dose
80 mg
Investigational Product Name
TAGRISSO 40 mg film-coated tablets
Active Substance
OSIMERTINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
oral
Authorisation Status
Authorised (marketing authorisation number EU/1/16/1086/003)
Starting Dose
40 mg
Dose Levels
40 mg
Frequency
once daily
Maximum Dose
80 mg
Investigational Product Name
PLACEBO
Modality
Other
Frequency
once daily

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