Treatment of Squamous Cell Carcinomas in the Head and Neck Area with a Maximum of Five Metastases with Pembrolizumab and Radiation Therapy: A Randomized Phase 3 Study (Study Name Abbreviation: PROLoNg)
Descrizione riassuntiva dello studio
Cancers in the head and neck area primarily occur in individuals over the age of 50. The symptoms mainly depend on the location of the tumor, such as in the oral cavity, throat, or larynx. Various treatment options are available, including surgery, radiation, chemotherapy, or immunotherapy. In this international study, we investigate the treatment of individuals with squamous cell carcinoma in the head and neck area when the cancer has already formed a few metastases (tumor deposits) in other organs, such as in the bones or lungs. The administration of the drug Pembrolizumab is the standard therapy in this situation. Despite the medication, the disease progresses in almost all affected individuals. We want to know whether additional precise high-dose radiation of the metastases can help delay the progression of the disease and possibly extend the lifespan of the affected individuals. In the study, we examine the combination of Pembrolizumab and high-dose targeted radiation therapy in individuals with at least one and a maximum of five metastases that can be irradiated. Pembrolizumab is approved in Switzerland for the treatment of various cancers. Participants in the study are randomly assigned to two groups (randomization) to obtain reliable study results. Participants in the two groups receive different treatments: Group 1 (Standard Treatment): Individuals receive Pembrolizumab for 2 years Group 2 (Study Treatment): The metastases are initially irradiated. After completing radiation therapy, participants receive Pembrolizumab for 2 years For both groups, palliative radiation of the primary tumor or metastases causing symptoms such as pain is possible at any time.
(BASEC)
Intervento studiato
All participants receive an infusion of the drug Pembrolizumab every six weeks for two years. Pembrolizumab is a medication that helps the body's immune system better recognize and fight cancer cells. It works by releasing a specific 'brake' (PD-1) on the body's immune cells, allowing them to act more actively against the tumor. The first Pembrolizumab infusion should take place as soon as possible after the study begins – but no later than six weeks.
Participants in Group 2 receive targeted high-precision radiation (SABR) for the metastases in addition to the treatment with Pembrolizumab. SABR stands for 'stereotactic ablative radiation therapy.' This is a particularly precise form of radiation where individual tumor foci (metastases) are treated with a high radiation dose – without significantly affecting surrounding healthy tissue. The treatment usually takes place in a few sessions and is often possible on an outpatient basis.
Before radiation, a CT scan is performed for planning to ensure that the metastases can be irradiated. The first radiation must occur within ten days after the CT and be completed before the first Pembrolizumab infusion. This infusion should then take place within 1 to 14 days after radiation – and no later than six weeks after the study begins. The goal is to time the two treatments well together so that they can work as effectively as possible.
(BASEC)
Malattie studiate
Squamous Cell Carcinoma in the Head and Neck Area with Metastases (max. five)
(BASEC)
- All genders, age at least 18 years - New or previously diagnosed and confirmed case of a so-called 'squamous cell carcinoma' of the mouth, throat, or larynx and currently 1-5 metastases (tumor deposits) - PD-L1-CPS of at least 1 (this is a characteristic of the tumor determined by the pathologist under a microscope using a method called immunohistochemistry) - No prior treatment of the metastases (BASEC)
Criteri di esclusione
- Rarer primary tumors of the head and neck region, such as those of the nasopharynx and salivary glands - Growth of a locally confined primary tumor in the head and neck area within 6 months after radiation in a previous treatment. - Already known immunosuppression (weakening of the immune system) (BASEC)
Luogo dello studio
Aarau, Basilea, Bellinzona, Berna, Chur, Lugano, Luzern, San Gallo, Winterthur, Zurigo, Altro
(BASEC)
Grabs, Locarno, Mendrisio, Uznach, Wil
(BASEC)
Sponsor
EORTC, Brussels, Belgium Swiss Cancer Institute, Bern
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Krista Zackel
+41 31 389 91 91
trials@clutterswisscancerinstitute.chSwiss Cancer Institute
(BASEC)
Informazioni generali
University of Zurich,Clinicque Universitarie Saint Luc,
+32 2 774 16 11
eortc@eortc.org(ICTRP)
Informazioni generali
University of ZurichClinicque Universitarie Saint Luc
+32 2 774 16 11
eortc@eortc.org(ICTRP)
Informazioni scientifiche
University of Zurich,Clinicque Universitarie Saint Luc,
+32 2 774 16 11
eortc@eortc.org(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
20.01.2026
(BASEC)
ID di studio ICTRP
NCT05815927 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
EORTC PROLoNg PROLoNg: Pembrolizumab and Radiotherapy for OLigometastatic squamous cell carcinoma of the head and Neck: a randomized phase III study (BASEC)
Titolo accademico
Pembrolizumab and Radiotherapy for OLigometastatic Squamous Cell Carcinoma of the Head and Neck: a Randomized Phase III Study (ICTRP)
Titolo pubblico
Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer (ICTRP)
Malattie studiate
Oligometastatic Squamous Cell Carcinoma of the Head and Neck (ICTRP)
Intervento studiato
Drug: PembrolizumabRadiation: stereotattic ablation radiotherapy (SABR) (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
Main inclusion Criteria:
- Male/female participants who are at least 18 years of age on the day of signing
informed consent
- Histologically confirmed HNSCC of the oral cavity, oropharynx, hypopharynx, larynx
or cervical primary occult and histologically or radiologically confirmed
oligometastatic disease. Histological characterization of one metastatic lesion is
strongly recommended.
- Patients with synchronous or metachronous oligometastatic disease according to the
ESTRO/EORTC consensus (1-5 metastatic lesions, with or without primary/recurrent
primary tumour and/or regional disease).
- Amenable to first-line systemic treatment for R/M SCCHN.
- For patients with oropharyngeal cancer: HPV status using p16 IHC evaluated locally.
- PD-L1 CPS of at least 1 as evaluated locally.
- Staging not older than 12 weeks before enrolment.
- All the 1-5 metastases must be amenable to SABR.
- Eligible for treatment with pembrolizumab.
- Have measurable disease based on RECIST 1.1.
- ECOG performance status of 0 to 1.
- Participants must have recovered from all treatment-related toxicities to baseline
or grade <=1, such as from previous radiotherapy, systemic treatment or surgery, and
not requiring corticosteroids for managing treatment-related side effects.
- Adequate Organ Function Laboratory Values.
- Before patient registration/enrolment, written informed consent must be given
according to ICH/GCP, and national/local regulations.
Main exclusion Criteria:
- Nasopharynx, sino-nasal, and salivary gland cancers are excluded.
- In-field progression in < 6 months after curative intended locoregional irradiation
of the head and neck.
- Lesions larger than 6 cm in the largest dimension as measured in the diagnostic CT
or MRI scan for lesions outside the brain. Note: bone metastases over 6 cm may be
included if in the opinion of the local radiation oncologist they can be treated
safely and no inner organ is affected.
- Brain metastases only.
- Has received any previous radiotherapy to any of the 1-5 metastases that would be
subject to SABR in the experimental arm unless the investigator agrees to treat only
after discussion with the RTQA team.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention.
- Previously treated brain metastases that are radiologically non-stable. Patients
with previously treated brain metastases, i.e., without evidence of progression for
at least 4 weeks by repeat imaging, clinically stable and without requirement of
steroid treatment for at least 14 days prior to first dose of study intervention,
can participate.
- Known contraindication to imaging tracer or any product of contrast media and MRI
contraindications. (ICTRP)
non disponibile
Endpoint primari e secondari
Progression-free survival by RECIST 1.1 (ICTRP)
Overall survival;Disease-specific survival;Time to disease progression;Time to development of new metastatic lesions;Time to progression in oligometastatic lesions initially present at enrolment;Adverse events according to CTCAE version 5.0;Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaire;Health-related quality of life evaluated using self-administered EORTC QLQ-HN43 questionnaire;Health-related quality of life evaluated using self-administered EORTC IL-198 questionnaire (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
Swiss Cancer Institute;Merck Sharp & Dohme LLC (ICTRP)
Contatti aggiuntivi
Panagiotis Belermpas, MD;Jean-Pascal Machiels, MD;EORTC HQ, eortc@eortc.org, +32 2 774 16 11, University of Zurich,Clinicque Universitarie Saint Luc, (ICTRP)
ID secondari
2023-504478-39-00, EORTC-2014-HNCG (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT05815927 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile