PRophylactic Cerebral Irradiation or Active MAgnetic Resonance Imaging Surveillance in Small-cell Lung Cancer Patients (PRIMALung Study)

NCT04790253 | Recruiting DMC

• 1 other identifier: EORTC-1901-LCG
• Study Type: interventional
• Target: 600
• Locations: 9 countries
• Sites: 41

Brief 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 surveillance in the entire study population.

Conditions

Limited Stage Small Cell Lung Cancer; Extensive-stage Small-cell Lung Cancer

Keywords

Prophylactic cerebral Irradiation; small cell lung cancer; PCI

Outcome Measures

Primary Outcomes (1)

• 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

  12 Months

Secondary Outcomes (3)

• cognitive failure free survival

  12 Months

• Quality of Life

  12 Months

• Safety profiling

  12 Months

Study Arms (2)

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.

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.

Interventions

Prophylactic cranial irradiation RADIATION

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.

PCI followed by brain MR surveillance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• UNICANCER: collaborator

Study Sites (41)

Medical University of Graz - Radio-oncology

Graz, 8036, Austria

RECRUITING

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

RECRUITING

AZ Groeninge Kortrijk - Campus Kennedylaan

Kortrijk, 8500, Belgium

RECRUITING

C.H.U. Sart-Tilman

Liège, 4000, Belgium

RECRUITING

Gasthuiszusters van Antwerpen - GasthuisZusters Antwerpen - Sint-Augustinus

Wilrijk, 2610, Belgium

RECRUITING

Institut Sainte Catherine (UNICANCER)

Avignon, 84918, France

RECRUITING

Centre D'Onco. & Radioth. De Haute Energie Du Pays Basque (UNICANCER)

Bayonne, 64100, France

RECRUITING

Institut Bergonie (UNICANCER)

Bordeaux, 33067, France

RECRUITING

Centre Francois Baclesse (CLCC) (UNICANCER)

Caen, 14076, France

RECRUITING

CHU de Dijon - Centre Georges-Francois-Leclerc (UNICANCER)

Dijon, 21079, France

RECRUITING

Centre Hospitalier Departemental Vendee (UNICANCER)

La Roche-sur-Yon, 85925, France

RECRUITING

Institut Paoli-Calmettes (UNICANCER)

Marseille, 13237, France

NOT YET RECRUITING

Institut du Cancer de Montpellier (UNICANCER)

Montpellier, 34298, France

RECRUITING

Centre Catalan d'Oncologie (UNICANCER)

Perpignan, 66000, France

RECRUITING

CHU de Lyon - Hopital Lyon Sud (UNICANCER)

Pierre-Bénite, 69495, France

RECRUITING

Centre Henri Becquerel (UNICANCER)

Rouen, 76038, France

RECRUITING

Institut de Cancerologie Strasbourg Europe (UNICANCER)

Strasbourg, 67200, France

RECRUITING

Gustave Roussy (UNICANCER)

Villejuif, 94805, France

RECRUITING

Universitaetsklinikum Aachen AOR - Medizinische Fakultaet der RWTH

Aachen, 52074, Germany

NOT YET RECRUITING

IRCCS Azienda Ospedaliera Universitaria San Martino "IST" - IRCCS - AUO San Martino - IST

Genova, 16132, Italy

NOT YET RECRUITING

ULSS 9 Scaligera Veneto - Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital

Legnago, 37045, Italy

NOT YET RECRUITING

Fondazione IRCCS - Policlinico San Matteo

Pavia, 27100, Italy

NOT YET RECRUITING

ASST-Bergamo Ospedale Treviglio-Caravaggio

Treviglio, 24047, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma

Verona, 37134, Italy

NOT YET RECRUITING

Medical University Of Gdansk

Gdansk, 80 211, Poland

NOT YET RECRUITING

Regional Cancer Centre

Olsztyn, 10 228, Poland

RECRUITING

Hospital Universitario Badajoz

Badajoz, 06080, Spain

NOT YET RECRUITING

Hospital Insular De Gran Canaria

Las Palmas de Gran Canaria, 35016, Spain

NOT YET RECRUITING

Hospital Universitario Puerta De Hierro

Majadahonda, 28222, Spain

RECRUITING

Inselspital

Bern, 3010, Switzerland

RECRUITING

Reseau Hospitalier Neuchatelois - RHNe - La Chaux de Fonds

La Chaux-de-Fonds, 2303, Switzerland

RECRUITING

Kantonsspital St Gallen

Sankt Gallen, 9007, Switzerland

RECRUITING

UniversitaetsSpital Zurich

Zurich, 8091, Switzerland

RECRUITING

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre

Bristol, BS2 8ED, United Kingdom

RECRUITING

NHS Lothian - Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

NOT YET RECRUITING

Maidstone & Tunbridge Wells NHS Trust - Maidstone Hospital

Maidstone, ME16 9QQ, United Kingdom

NOT YET RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

NOT YET RECRUITING

Royal Marsden Hospital - Sutton

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Corinne Faivre-Finn, MD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Antonin Levy, MD

  Centre Gustave Roussy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

EORTC Reception

CONTACT

+3227741611; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 10, 2021
• Study Start: October 27, 2022
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: November 3, 2023

Record last verified: 2023-11

Locations

ES (3); CH (4); AU (1); FR (13); BE (5); DE (1); PL (2); IT (5); GB (7)