Clinical trial • Phase III • Oncology|Respiratory
Durvalumab for Resectable non-small cell lung cancer (stage IIB–IIIB, N2)
Phase III trial of Durvalumab for Resectable non-small cell lung cancer (stage IIB–IIIB, N2).
Overview
- Trial Therapeutic Area
- Oncology|Respiratory
- Trial Disease
- Resectable non-small cell lung cancer (stage IIB–IIIB, N2)
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody|Small molecule
Key dates
- Initial CTIS Submission Date
- 21-05-2024
- First CTIS Authorization Date
- 10-09-2024
Trial design
Randomised, open-label, control arm: observation (no adjuvant durvalumab). experimental arm (adjuvant): durvalumab 1500 mg iv every 4 weeks (±1 week) until relapse or unacceptable toxicity, maximum of 12 cycles after surgery. note: neoadjuvant phase (pre-randomisation) includes durvalumab 1500 mg iv every 3 weeks (±1 week) for 3-4 cycles plus chemotherapy every 3 weeks (±1 week) for 3-4 cycles for all patients. Phase III trial in Estonia, Austria, Ireland and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Control arm: observation (no adjuvant durvalumab). Experimental arm (adjuvant): durvalumab 1500 mg IV every 4 weeks (±1 week) until relapse or unacceptable toxicity, maximum of 12 cycles after surgery. Note: neoadjuvant phase (pre-randomisation) includes durvalumab 1500 mg IV every 3 weeks (±1 week) for 3-4 cycles plus chemotherapy every 3 weeks (±1 week) for 3-4 cycles for all patients.
- Target Sample Size
- 245
- Trial Duration For Participant
- 1977
Eligibility
Recruits 245 Vulnerable population flag selected. Adults only (Age ≥18). Patients with psychiatric illness or social situations that would limit compliance or compromise ability to give written informed consent are excluded. Written informed consent is required from the participant (no paediatric/assent process described). Subject information and informed consent forms (ICFs) exist in multiple language versions (EN, FR, DE, IT, NL) as provided in the submitted documents..
- Pregnancy Exclusion
- Female patients who are pregnant or in the period of lactation.
- Vulnerable Population
- Vulnerable population flag selected. Adults only (Age ≥18). Patients with psychiatric illness or social situations that would limit compliance or compromise ability to give written informed consent are excluded. Written informed consent is required from the participant (no paediatric/assent process described). Subject information and informed consent forms (ICFs) exist in multiple language versions (EN, FR, DE, IT, NL) as provided in the submitted documents.
Inclusion criteria
- {"criterion_text":"- Histologically confirmed NSCLC.\n- Primary tumour resectable and functionally operable as assessed per local multidisciplinary tumour board (cardiac evaluation, pulmonary function and diffusion capacity, comorbidity).\n- Patient has to be fit to receive at least one of the protocol-defined platinum-based chemotherapy regimens, as per local standards.\n- Stage IIB-IIIB (T1-4 N0-2) according to 8th edition of the TNM staging system of lung cancer. Stage III assessment should include samples of lymph nodes at levels 4, bilaterally, and level 7 to rule out stage IIIB N3 disease. T4 tumours will only be eligible if they are defined as T4 based only on their size (>7cm); any other reason will be considered ineligible.\n- Known PD-L1 status, as tested locally using a validated assay.\n- Absence of EGFR mutation or ALK translocation, as tested locally.\n- Adequate haematological, renal, and liver function.\n- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n- Age ≥18 at the time of enrolment.\n- Body weight >30 kg.\n- Life expectancy of at least 12 weeks."}
Exclusion criteria
- {"criterion_text":"- T4 with invasion of heart, great vessels, carina, trachea, oesophagus, or spine.\n- 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.\n- Female patients who are pregnant or in the period of lactation.\n- Any previous or concurrent treatments for NSCLC.\n- Any previous immunotherapy.\n- Major surgical procedure (as per investigators assessment) within 28 days before enrolment.\n- History of allogenic organ transplantation.\n- Active or prior documented autoimmune disease or inflammatory disorders\n- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease (ILD) or serious chronic gastrointestinal conditions associated with diarrhoea.\n- Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.\n- History of another primary malignancy.\n- History of leptomeningeal carcinomatosis.\n- History of active primary immunodeficiency.\n- Active hepatitis infection.\n- Known HIV infection that is not well-controlled.\n- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.\n- Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab.\n- Concurrent enrolment in another interventional clinical trial.\n- Known allergy or suspected hypersensitivity to durvalumab or its excipients."}
Endpoints
Primary endpoints
- {"endpoint_text":"- DFS in patients without pCR, measured from randomisation.","definition_or_measurement_approach":"Disease-free survival (DFS) measured from randomisation in patients who do not achieve complete pathological response (pCR) as per local assessment according to IASLC recommendations."}
Secondary endpoints
- {"endpoint_text":"- Assessed in the adjuvant treatment phase (after randomisation) • DFS in patients with pCR. • Overall survival (OS) in patients with/without pCR, ITT. • DFS in patients with/without ctDNA clearance. • Time to recurrence (TTR) in patients with/without pCR, ITT. • Time to treatment discontinuation (TTD) in patients with/without pCR, ITT. • Toxicity according to CTCAE v5.0.","definition_or_measurement_approach":"Endpoints assessed in the adjuvant treatment phase after randomisation; toxicity graded according to CTCAE v5.0; DFS/OS/TTR/TTD evaluated in specified subgroups (pCR status, ctDNA clearance) and ITT where stated."}
- {"endpoint_text":"- Key secondary endpoint: (hierarchically tested) DFS in the ITT cohort (with and without pCR), measured from randomisation.","definition_or_measurement_approach":"DFS measured from randomisation in the intention-to-treat (ITT) cohort (including patients with and without pCR); hierarchical testing specified for this key secondary endpoint."}
Recruitment
- Planned Sample Size
- 245
- Recruitment Window Months
- 65
- Consent Approach
- Written informed consent required from adult participants (age ≥18). ICFs and subject information materials provided in multiple languages (documents available in EN, FR, DE, IT, NL). Patients unable to provide written informed consent (e.g. due to psychiatric illness/social situations limiting capacity) are excluded.
Geography
- Total Number Of Sites
- 17
- Total Number Of Participants
- 335
Estonia
- Earliest CTIS Part Ii Submission Date
- 28-08-2024
- Latest Decision Or Authorization Date
- 16-09-2024
- Processing Time Days
- 19
- Number Of Sites
- 1
- Number Of Participants
- 30
Sites
- Site Name
- North Estonia Medical Centre Foundation
- Department Name
- Clinic of Oncology and Haematology, Department of Chemotherapy
- Contact Person Name
- Kersti Oselin
- Contact Person Email
- kersti.oselin@regionaalhaigla.ee
Austria
- Earliest CTIS Part Ii Submission Date
- 21-08-2024
- Latest Decision Or Authorization Date
- 15-09-2024
- Processing Time Days
- 25
- Number Of Sites
- 1
- Number Of Participants
- 25
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Department of Thoracic Surgery
- Contact Person Name
- Clemens Aigner
- Contact Person Email
- clemens.aigner@meduniwien.ac.at
Ireland
- Earliest CTIS Part Ii Submission Date
- 19-03-2025
- Latest Decision Or Authorization Date
- 02-05-2025
- Processing Time Days
- 44
- Number Of Sites
- 2
- Number Of Participants
- 30
Sites
- Site Name
- St James's Hospital
- Department Name
- Medical oncology
- Contact Person Name
- Forde Patrick
- Contact Person Email
- PaForde@stjames.ie
- Site Name
- Beaumont Hospital
- Department Name
- Medical Oncology
- Contact Person Name
- Jarushka Naidoo
- Contact Person Email
- jarushkanaidoo@beaumont.ie
Netherlands
- Earliest CTIS Part Ii Submission Date
- 16-04-2025
- Latest Decision Or Authorization Date
- 06-05-2025
- Processing Time Days
- 20
- Number Of Sites
- 2
- Number Of Participants
- 30
Sites
- Site Name
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Department Name
- Medical Oncology
- Contact Person Name
- Wilhelmina Sabina Marilyn Emilie Theelen
- Contact Person Email
- w.theelen@nki.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Medical Oncology
- Contact Person Name
- Wouter De Jong
- Contact Person Email
- w.k.dejong-9@umcutrecht.nl
Belgium
- Earliest CTIS Part Ii Submission Date
- 12-08-2024
- Latest Decision Or Authorization Date
- 19-09-2024
- Processing Time Days
- 38
- Number Of Sites
- 2
- Number Of Participants
- 60
Sites
- Site Name
- Institut Jules Bordet
- Department Name
- Medical Oncology
- Contact Person Name
- Mariana Brandao
- Contact Person Email
- mariana.brandao@hubruxellles.be
- Site Name
- Antwerp University Hospital
- Department Name
- Thoracic ongology
- Contact Person Name
- Reinier Wener
- Contact Person Email
- reinier.wener@uza.be
France
- Earliest CTIS Part Ii Submission Date
- 10-07-2024
- Latest Decision Or Authorization Date
- 16-09-2024
- Processing Time Days
- 68
- Number Of Sites
- 4
- Number Of Participants
- 80
Sites
- Site Name
- Centre Leon Berard
- Department Name
- Medical Oncology
- Contact Person Name
- Maurice Perol
- Contact Person Email
- maurice.perol@lyon.unicancer.fr
- Site Name
- Centre Hospitalier Universitaire D'Angers
- Department Name
- Pneumology
- Contact Person Name
- Youssef Oulkhouir
- Contact Person Email
- youssef.oulkhouir@chu-angers.fr
- Site Name
- Centre Hospitalier Le Mans
- Department Name
- Pneumology
- Contact Person Name
- Camille Guguen
- Contact Person Email
- cguguen@ch-lemans.fr
- Site Name
- Institut Bergonie
- Department Name
- Medical Oncology
- Contact Person Name
- Sophie Cousin
- Contact Person Email
- s.cousin@bordeaux.unicancer.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 26-08-2024
- Latest Decision Or Authorization Date
- 12-09-2024
- Processing Time Days
- 17
- Number Of Sites
- 5
- Number Of Participants
- 80
Sites
- Site Name
- Istituto Oncologico Veneto
- Department Name
- Medical Oncology
- Contact Person Name
- Laura Bonanno
- Contact Person Email
- laura.bonanno@iov.veneto.it
- Site Name
- I.F.O. Istituti Fisioterapici Ospitalieri
- Department Name
- Medical Oncology 2
- Contact Person Name
- Lorenza Landi
- Contact Person Email
- lorenza.landi@ifo.it
- Site Name
- Azienda Ospedaliera Universitaria Senese
- Department Name
- U.O.C. Immunoterapia Oncologica
- Contact Person Name
- Michele Maio
- Contact Person Email
- mmaiocro@gmai.com
- Site Name
- Azienda Ospedaliera Universitaria Integrata Verona
- Department Name
- Oncology
- Contact Person Name
- Lorenzo Belluomini
- Contact Person Email
- lorenzo.belluomini@univr.it
- Site Name
- Azienda Ospedaliero-Universitaria Ss Antonio E Biagio E Cesare Arrigo
- Department Name
- Medical Oncology
- Contact Person Name
- Pier Luigi Piovano
- Contact Person Email
- plpiovano@ospedale.al.it
Sponsor
Primary sponsor
- Full Name
- ETOP IBCSG Partners Foundation
- Organisation Type
- Laboratory/Research/Testing facility
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Fisher Clinical Services GmbH
- Responsibilities
- Secondary packaging of the durvalumab vials and study specific labeling; EU QP release of the final, labelled study drugs; distribution to participating clinical trial sites
Third parties
- {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Secondary packaging of the durvalumab vials and study specific labeling","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"EU QP release of the final, labelled study drugs","organisation_type":"Pharmaceutical company"}
- {"country":"Greece","full_name":"Frontier Science Foundation-Hellas","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Distribution to participating clinical trial sites","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Centre Hospitalier Universitaire Vaudois","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- IMFINZI 50 mg/mL concentrate for solution for infusion.
- Active Substance
- Durvalumab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Marketing authorisation (EU) EU/1/18/1322/001
- Starting Dose
- 1500 mg
- Dose Levels
- 1500 mg (no escalation described)
- Frequency
- Neoadjuvant: every 3 weeks (±1 week) for 3-4 cycles; Adjuvant: every 4 weeks (±1 week) up to 12 cycles
- Maximum Dose
- 1500 mg (max daily dose amount reported); max total dose amount 24000 mg
- Investigational Product Name
- PEMETREXED
- Active Substance
- Pemetrexed disodium
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised medicinal product (prodAuthStatus=2)
- Starting Dose
- 500 mg/m2 (max daily dose amount reported)
- Dose Levels
- 500 mg/m2 (no escalation described)
- Frequency
- Every 3 weeks (as per neoadjuvant chemotherapy schedule)
- Maximum Dose
- Max total dose amount 2000 mg/m2
- Investigational Product Name
- GEMCITABINE
- Active Substance
- Gemcitabine hydrochloride
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised medicinal product (prodAuthStatus=2)
- Starting Dose
- 1250 mg/m2 (max daily dose amount reported)
- Dose Levels
- 1250 mg/m2 (no escalation described)
- Frequency
- Every 3 weeks (as per neoadjuvant chemotherapy schedule)
- Maximum Dose
- Max total dose amount 5000 mg/m2
- Investigational Product Name
- PACLITAXEL
- Active Substance
- Paclitaxel
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised medicinal product (prodAuthStatus=2)
- Starting Dose
- 200 mg/m2 (max daily dose amount reported)
- Dose Levels
- 200 mg/m2 (no escalation described)
- Frequency
- Every 3 weeks (as per neoadjuvant chemotherapy schedule)
- Maximum Dose
- Max total dose amount 800 mg/m2
- Investigational Product Name
- CISPLATIN
- Active Substance
- Cisplatin
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised medicinal product (prodAuthStatus=2)
- Starting Dose
- 75 mg/m2 (max daily dose amount reported)
- Dose Levels
- 75 mg/m2 (no escalation described)
- Frequency
- Every 3 weeks (as per neoadjuvant chemotherapy schedule)
- Maximum Dose
- Max total dose amount 300 mg/m2
- Investigational Product Name
- CARBOPLATIN
- Active Substance
- Carboplatin
- Modality
- Small molecule
- Routes Of Administration
- Intravenous infusion
- Route
- Intravenous infusion
- Authorisation Status
- Authorised medicinal product (prodAuthStatus=2)
- Starting Dose
- AUC 6 (max daily dose amount reported as '6' with doseUom 'Other')
- Dose Levels
- AUC 6 (no escalation described)
- Frequency
- Every 3 weeks (as per neoadjuvant chemotherapy schedule)
- Maximum Dose
- Max total dose amount 24 (doseUom 'Other')
- Combination Treatment
- Yes
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