Limited Stage Small Cell Lung CancerPRIMALungNCT04790253
PRophylactic Cerebral Irradiation or Active MAgnetic Resonance Imaging Surveillance in Small-cell Lung Cancer Patients (PRIMALung Study)
A study testing Prophylactic cranial irradiation in people with Limited Stage Small Cell Lung Cancer and Extensive-stage Small-cell Lung Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 55 sites in 9 countries.
Trial summary
In this phase III study, the primary objective is to test with a one-sided significance of 5% whether for the treatment of small cell lung cancer (SCLC) patients, brain MRI surveillance alone is non-inferior in terms of overall survival compared to prophylactic cranial irradiation (PCI) combined with brain MRI… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Limited Stage Small Cell Lung Cancer, Extensive-stage Small-cell Lung Cancer
- What is being tested?
- Prophylactic cranial irradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 55 sitesin 9 countries
- Study dates
- 27 Oct 2022to Apr 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Histologically/cytologically proven diagnosis of SCLC
- Limited and extensive stage
- LS SCLC: Stage I-III (T any, N any, M0, according to UICC TNM staging v8.0) that can be safely treated with definitive radiation doses. Excludes T3-4 due to multiple lung nodules that are too extensive or have tumour/nodal volume that is too large to be encompassed in a tolerable radiation plan.
- ES SCLC: Stage IV (T any, N any, M 1a/b), or T3-4 due to multiple lung nodules that are too extensive or have tumour/nodal volume that is too large to be encompassed in a tolerable radiation plan.
- Completed standard therapy prior to randomization:
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- For patients with LS-SCLC, this includes a combination of 4-6 cycles of platinum-based doublet chemotherapy and either definitive thoracic radiotherapy (including SBRT for early-stage T1-2 N0 M0 disease who do not undergo surgery) or definitive surgical resection; thoracic radiation in addition to definitive surgical resection is allowed at the discretion of the treating physician, but is not mandated.
- For patients with ES-SCLC, this includes 4-6 cycles of platinum-based doublet chemotherapy either with or without thoracic radiotherapy
- o Immunotherapy concurrent with and/or adjuvant to standard therapy is allowed at the discretion of the treating physician.
- Absence of progressive disease after completed standard therapy on systemic imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of Chest/Abdomen/Pelvis and brain MRI), 28 days before randomization.
- Absence of brain metastases or leptomeningeal disease after completed standard therapy on systemic imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of Chest/Abdomen/Pelvis and brain MRI), within 28 days before randomization.
- Interval from day 1 of last cycle of chemotherapy to randomization of ≤8 weeks
- ECOG PS ≤ 2
- Estimated creatinine clearance ≥ 30 mL/min as calculated using the MDRD formula
- Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
- Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antioestrogens, low body weight, ovarian suppression or other reasons.
- Patients Women of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the entire period of the radiotherapy treatment study participation and for at least 30 days after the last dose of radiotherapy. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
- Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
- Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
- Female subjects who are breast feeding should discontinue nursing prior to the first dose of radiotherapy and during the entire period of the radiotherapy treatmentuntil 30 days after the administration of the last dose of radiotherapy.
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Who cannot join
- Prior radiotherapy to the brain or whole brain radiotherapy. Note: Patients who have undergone prior stereotactic radiosurgery for benign tumours or conditions (e.g., acoustic neuroma, grade I meningioma, trigeminal neuralgia) may be considered on a case-by-case basis. Discussion with EORTC Headquarters is mandatory, before the randomization.
- Known contraindication to imaging tracer or any product of contrast media, such as allergy or insufficient renal function. Known contraindication to MRI, such as implanted metal devices or foreign bodies.
- Other active hematologic or solid tumour malignancy requiring current active treatment.
- Any unresolved toxicities from prior therapy (e.g., chemotherapy, radiotherapy) greater than CTCAE grade 2 (according to CTCAE v5.0) at the time of randomization.
- Patient with severe active comorbidities, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to randomization
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- Transmural myocardial infarction within 6 months prior to randomization
- Acute infection requiring treatment at the time of randomization
- Chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy at the time of randomization
- Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease
- HIV positive with CD4 count < 200 cells/microliter. Note: patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 16 weeks prior to randomization.
- Any severe comorbidity that in the opinion of the Investigator might hamper the participation to the study and/or the treatment administration.
- Severe neurological (including dementia and epilepsy) or psychiatric disorder requiring active treatment.
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
Trial locations and contacts
55 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
55 sites in 9 countries
France27 sites, 27 recruiting
- Recruiting
Institut de Cancerologie de l Ouest (ICO) - Angers
Angers, FR 49055
- Recruiting
Institut Sainte Catherine (UNICANCER)
Avignon, 84918
- Recruiting
Centre D'Onco. & Radioth. De Haute Energie Du Pays Basque (UNICANCER)
Bayonne, 64100
- Recruiting
Institut Bergonie (UNICANCER)
Bordeaux, 33067
- Recruiting
Centre Francois Baclesse (CLCC) (UNICANCER)
Caen, 14076
- Recruiting
Centre Hospitalier Metropole Savoie
Chambéry, FR 73000
- Recruiting
Centre Hospitaliler Cholet
Cholet, FR 49325
- Recruiting
Centre Hopitalier Intercommunal De Creteil
Créteil, FR 94010
- Recruiting
CHU de Dijon - Centre Georges-Francois-Leclerc (UNICANCER)
Dijon, 21079
- Recruiting
Centre Hospitalier Departemental Vendee (UNICANCER)
La Roche-sur-Yon, 85925
- Recruiting
Centre Oscar Lambret
Lille, FR 59020
- Recruiting
Centre Hospitalier Bretagne Sud - Site du Scorff
Lorient, FR 56322
- Recruiting
Institut Paoli-Calmettes (UNICANCER)
Marseille, 13237
- Recruiting
Institut du Cancer de Montpellier (UNICANCER)
Montpellier, 34298
- Not yet recruiting
Assistance Publique Hopitaux Paris- APHP - APHP Sorbonne Univ - Hopital la Pitie-Salpetriere
Paris, FR 75013
- Not yet recruiting
Institut Curie- Hopital de Paris
Paris, FR 75248
- Recruiting
Centre Catalan d'Oncologie (UNICANCER)
Perpignan, 66000
- Recruiting
Centre Catalan d'Oncologie
Perpignan, FR 66000
- Recruiting
CHU de Lyon - Hopital Lyon Sud (UNICANCER)
Pierre-Bénite, 69495
- Recruiting
Centre Henri Becquerel (UNICANCER)
Rouen, 76038
- Not yet recruiting
Hospi Grand Ouest - Clinique Mutualiste de l'Estuaire
Saint-Nazaire, FR 44600
- Not yet recruiting
CHU Saint-Etienne - Hopital Nord
Saint-Priest-en-Jarez, FR 42270
- Recruiting
Institut de Cancerologie Strasbourg Europe (UNICANCER)
Strasbourg, 67200
- Recruiting
Polyclinique de l'Ormeau
Tarbes, FR 65000
- Recruiting
Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, FR 54519
- Recruiting
Centre d'Oncologie Saint-Yves
Vannes, FR 56000
- Recruiting
Gustave Roussy (UNICANCER)
Villejuif, 94805
United Kingdom7 sites, 7 recruiting
- Recruiting
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Bristol, BS2 8ED
- Not yet recruiting
NHS Lothian - Western General Hospital
Edinburgh, EH4 2XU
- Recruiting
Maidstone & Tunbridge Wells NHS Trust - Maidstone Hospital
Maidstone, ME16 9QQ
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
- Recruiting
Nottingham University Hospitals NHS Trust - City Hospital
Nottingham, NG5 1PB
- Recruiting
Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital
Sheffield, S10 2SJ
- Recruiting
Royal Marsden Hospital - Sutton
Sutton, SM2 5PT
Belgium5 sites, 4 recruiting
- Recruiting
Institut Jules Bordet
Anderlecht, 1070
- Recruiting
Universitair Ziekenhuis Antwerpen
Edegem, 2650
- Recruiting
AZ Groeninge Kortrijk - Campus Kennedylaan
Kortrijk, 8500
- Terminated
C.H.U. Sart-Tilman
Liège, 4000
- Recruiting
Gasthuiszusters van Antwerpen - GasthuisZusters Antwerpen - Sint-Augustinus
Wilrijk, 2610
Italy5 sites, 5 recruiting
- Not yet recruiting
IRCCS Azienda Ospedaliera Universitaria San Martino "IST" - IRCCS - AUO San Martino - IST
Genova, 16132
- Not yet recruiting
ULSS 9 Scaligera Veneto - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
Legnago, 37045
- Not yet recruiting
Fondazione IRCCS - Policlinico San Matteo
Pavia, 27100
- Not yet recruiting
ASST-Bergamo Ospedale Treviglio-Caravaggio
Treviglio, 24047
- Not yet recruiting
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma
Verona, 37134
Switzerland4 sites, 4 recruiting
- Recruiting
Inselspital
Bern, 3010
- Recruiting
Reseau Hospitalier Neuchatelois - RHNe - La Chaux de Fonds
La Chaux-de-Fonds, 2303
- Recruiting
Kantonsspital St Gallen
Sankt Gallen, 9007
- Recruiting
UniversitaetsSpital Zurich
Zurich, 8091
Spain3 sites, 3 recruiting
- Not yet recruiting
Hospital Universitario Badajoz
Badajoz, 06080
- Not yet recruiting
Hospital Insular De Gran Canaria
Las Palmas de Gran Canaria, 35016
- Recruiting
Hospital Universitario Puerta De Hierro
Majadahonda, 28222
Poland2 sites, 2 recruiting
- Recruiting
Medical University Of Gdansk
Gdansk, 80 211
- Recruiting
Regional Cancer Centre
Olsztyn, 10 228
Austria1 site, 1 recruiting
- Recruiting
Medical University of Graz - Radio-oncology
Graz, 8036
Netherlands1 site, 1 recruiting
- Not yet recruiting
University Medical Center Groningen
Groningen, NL 9713 GZ
About this study
In this phase III study, the primary objective is to test with a one-sided significance of 5% whether for the treatment of small cell lung cancer (SCLC) patients, brain MRI surveillance alone is non-inferior in terms of overall survival compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance in the entire study population.
Read the detailed description
The primary objective is to test with a one-sided significance of 5% whether for the treatment of small cell lung cancer (SCLC) patients, brain MRI surveillance alone is non-inferior in terms of overall survival compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance in the entire study population under the treatment policy strategy.
The secondary objectives are:
- To test with a one-sided type I error of 2.5% whether brain MRI surveillance is superior in terms of cognitive failure free survival (CFFS) compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance in the study population.
- To test with a one-sided type I error of 2.5% whether brain MRI surveillance is superior in terms of global health status/QoL and cognitive functioning according to EORTC QLQ-C30 questionnaire compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance in the study population.
- To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms in the treated population (i.e. patients who have started treatment).
The exploratory objectives are:
- To compare OS and CFFS between the arms within the subgroups of patients with LS and ES disease.
- To compare OS and CFFS between the arms within the subgroups: HA-PCI or not, first-line immunotherapy or not, memantine or not.
- To compare cognitive failure free survival (CFFS) rate at 12 months after randomization between the arms.
- To compare the cumulative incidence of cognitive failures with death as a competing risk between the arms.
- To compare brain-metastasis-free survival (BMFS) between the arms.
- To compare progression free survival (PFS) between the arms.
- To compare time to brain-metastasis-attributed death (TBMAD) between the arms.
- To compare other QoL scales according to EORTC QLQ-C30 and QLQ-BN20 questionnaires between arms.
- To evaluate the cost-effectiveness of MRI surveillance alone versus MRI surveillance combined with PCI.
- To collect blood for biobanking.
- Being tested
- Prophylactic cranial irradiation
- Keywords
- Prophylactic cerebral Irradiation, small cell lung cancer, PCI
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prophylactic cranial irradiationRadiation
Prophylactic cranial irradiation (PCI) is a technique used to combat the occurrence of metastasis to the brain in highly aggressive cancers that commonly metastasize to brain, most notably small-cell lung cancer.
| Study group | Role | What they receive |
|---|---|---|
| PCI followed by brain MR surveillance | Active comparator | Prophylactic cranial irradiation will be delivered at the dose of 25 Gy in 10 fractions to the whole brain.
Patients must have a brain MRI performed within 28 days before randomisation and at 3, 6, 9, 12, 18 and 24 months.
Extracranial imaging is recommended and will be performed per institutional standards at the discretion of the treating physician. Receives: Radiation: Prophylactic cranial irradiation |
| MRI Active Surveillance | No intervention | Patients must have a brain MRI performed within 28 days before randomisation and at 3, 6, 9, 12, 18 and 24 month. Clinical evaluation will be performed every 3 months. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
The primary objective is to test with a one-sided significance of 5% whether for the treatment of small cell lung cancer (SCLC) patients, brain MRI surveillance alone is non-inferior in terms of overall survival compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance in the entire study population
Measured: 12 Months
Secondary outcomes (3)
cognitive failure free survival
To test with a one-sided type I error of 2.5% whether brain MRI surveillance is superior in terms of cognitive failure free survival (CFFS) compared to prophylactic cranial irradiation (PCI)
Measured: 12 Months
Quality of Life
To show that brain MRI surveillance is superior in terms of global health status/QoL and cognitive functioning according to EORTC QLQ-C30 questionnaire compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance
Measured: 12 Months
Safety profiling
To evaluate the frequency and severity of toxicities according to CTCAE v5.0 in the two arms in the treated population (i.e. patients who have started treatment).
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start27 Oct 2022
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Limited Stage Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- After eligibility checks, patients will be randomized between the 2 arms, and stratified by stage of disease (limited versus extensive), immunotherapy as part of the first-line treatment (yes/no), and ECOG Performance Status (0 or 1 versus 2).
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- UNICANCER
- Responsible party
- Sponsor
- Investigators
- Corinne Faivre-Finn, MD, Principal investigator, The Christie NHS Foundation TrustAntonin Levy, MD, Principal investigator, Centre Gustave Roussy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04790253
- Sponsor's protocol ID
- EORTC-1901-LCG
- Acronym
- PRIMALung
- Status last verified
- Oct 2026
- First submitted
- 5 Mar 2021
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No