Oligometastatic Squamous Cell Carcinoma of the Head and NeckPhase 3PROLoNgNCT05815927
Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer
A Phase 3 study testing Pembrolizumab and stereotattic ablation radiotherapy (SABR) in people with Oligometastatic Squamous Cell Carcinoma of the Head and Neck, run by European Organisation for Research and Treatment of Cancer - EORTC at 30 sites in 4 countries.
Trial summary
This is a randomized open-label multicentre phase III superiority study of the effect of adding SABR to the standard of care treatment pembrolizumab on progression free survival in patients with oligometastases of a squamous cell carcinoma of the head and neck (SCCHN), histological confirmation of the primary disease… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oligometastatic Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Pembrolizumab and stereotattic ablation radiotherapy (SABR)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 30 sitesin 4 countries
- Study dates
- 23 May 2025to 30 Mar 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
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.
Trial locations and contacts
30 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
30 sites in 4 countries
Spain9 sites, 9 recruiting
- Not yet recruiting
Institut Català d'Oncologia - Hospital Duran i Reynals
Badalona, 08916
- Not yet recruiting
Hospital Universitario De Cruces
Barakaldo, 48903
- Recruiting
Hospital Universitari Vall d'Hebron -Vall d'Hebron Institut Oncologia
Barcelona, 08035
- Recruiting
ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
Barcelona, 08908
- Recruiting
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, 35010
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
- Recruiting
Hospital Universitario San Carlos
Madrid, 28040
- Not yet recruiting
Hospital Universitario 12 De Octubre
Madrid, 28041
- Not yet recruiting
Hospital Universitario Virgen De La Victoria
Málaga, 29010
Italy8 sites, 8 recruiting
- Not yet recruiting
IRCCS--Ospedale Bellaria-Bologna
Bologna, 40139
- Not yet recruiting
Azienda Ospedaliera Santa Croce E Carle
Cuneo, 12100
- Recruiting
Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi
Florence, 50134
- Recruiting
Istituto Clinico Humanitas
Milan, 20089
- Recruiting
IRCCS - Fondazione Istituto Nazionale dei Tumori
Milan, 20133
- Not yet recruiting
Azienda Sanitaria Locale Napoli 1 Centro
Naples, 80147
- Not yet recruiting
AUSL Romagna - AUSL Della Romagna -Ospedale Santa Maria delle Croci
Ravenna, 48121
- Recruiting
Azienda ospedaliero Univ Policlinico Umberto I
Rome, 00161
Switzerland7 sites, 7 recruiting
- Not yet recruiting
Kantonsspital Aarau
Aarau, 5001
- Not yet recruiting
Oncology Institute of Southern Switzerland (IOSI) - Oncology Institute of Southern Switzerland - Ospedale San Giovanni
Bellinzona, 6500
- Recruiting
Inselspital - Inselspital
Bern, 3010
- Not yet recruiting
Kantonsspital Graubuenden
Chur, 7000
- Recruiting
Luzerner Kantonsspital
Lucerne, 6004
- Not yet recruiting
Kantonsspital Winterthur
Winterthur, 8401
- Recruiting
UniversitaetsSpital Zurich
Zurich, 8901
Belgium6 sites, 6 recruiting
- Recruiting
Cliniques Universitaires Saint-Luc
Brussels, 1200
- Not yet recruiting
CHU Helora Pole Hospitalier Jolimont - Hopital Jolimont
Haine-Saint-Paul, 7100
- Recruiting
AZ Groeninge Kortrijk - Campus Kennedylaan
Kortrijk, 8500
- Recruiting
CHU-UCL Namur - CHU Site Sainte-Elisabeth-UCL Namur
Namur, 5000
- Recruiting
VITAZ St Niklaas - VITAZ- Oncology
Sint-Niklaas, 9100
- Recruiting
Ziekenhuis aan de Stroom (ZAS) - ZAS Augustinus (previous GZA)
Wilrijk, 2610
About this study
Official title: Pembrolizumab and Radiotherapy for OLigometastatic Squamous Cell Carcinoma of the Head and Neck: a Randomized Phase III Study
This is a randomized open-label multicentre phase III superiority study of the effect of adding SABR to the standard of care treatment pembrolizumab on progression free survival in patients with oligometastases of a squamous cell carcinoma of the head and neck (SCCHN), histological confirmation of the primary disease at first diagnosis, and PD-L1 CPS ≥1. After eligibility check and signing informed consent, all patients will be prospectively enrolled in a 1:1 ratio between current standard of care treatment (pembrolizumab, Arm 1) vs. SABR + standard of care treatment (Arm 2) to oligometastases.
Any radical treatment to the synchronous primary/ recurrent primary tumor and/or involved cervical nodes (surgery or radiotherapy), as decided by the local tumor board/ treating physicians, should be completed prior to enrolment.Surgical removal of metastases is allowed for diagnostic purposes or for brain metastases, as long as these metastases count toward the total number of 5 and at least one metastasis is left for treatment with SABR. Such surgical procedures should be performed prior to enrolment.
- Being tested
- Pembrolizumab, stereotattic ablation radiotherapy (SABR)
- Keywords
- Pembrolizumab, Stereotactic ablative radiotherapy, oligometastatic HNSCC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab: 400mg Q6W up to 2 years (i.e 17 cycles).
stereotattic ablation radiotherapy (SABR)Radiation
Also called SBRT
Total dose and number of fractions will depend on the site of the disease. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments have to be completed within 10 working days.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 : Standard of Care | Active comparator | Pembrolizumab at a dose of 400mg every 6-weeks (Q6W) for a duration of 2 years (i.e 17 cycles) as per Standard of Care treatment of oligometastatic HNSCC disease. Palliative radiotherapy to oligometastatic disease is allowed if necessary as per standard of care to relieve symptomatic disease and prevent complications. Recommended dose regimens are 1x 8 Gy, 5x 4 Gy and 10x 3 Gy. Planning technique and target volume definition should be according to institutional standards.No ablative-stereotactic dose and no boost techniques are allowed with the exception of CNS-metastases treatment. Receives: Drug: Pembrolizumab |
| Arm 2 : Standard of Care + stereotattic ablative radiation (SABR) | Experimental | The Experiemnt Arm consists of pembrolizumab at a dose of 400mg every 6-weeks (Q6W) for a duration of 2 years (i.e 17 cycles) as per Standard of Care treatment of oligometastatic HNSCC disease in combination with SABR. For each oligometastatic lesion treatment, specific SABR fractions and targeted dose(Gy) should be used depending on the location of the lesion. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments have to be completed within 10 working days. Receives: Drug: Pembrolizumab; Radiation: stereotattic ablation radiotherapy (SABR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival by RECIST 1.1
To assess whether SABR added to pembrolizumab improves progression-free survival in patients with HNSCC disease, PD-L1 CPS ≥1 and 1-5 metastatic lesions, as compared to pembrolizumab alone.
Measured: 2.6 years after first patient in
Secondary outcomes (9)
Overall survival
To assess whether SABR added to pembrolizumab improves OS
Measured: 5.2 years after first patient in
Disease-specific survival
To assess whether SABR added to pembrolizumab improves disease-specific survival
Measured: 5.2 years after first patient in
Time to disease progression
To assess whether SABR added to pembrolizumab improves time to disease progression
Measured: 5.2 years after first patient in
Time to development of new metastatic lesions
To assess whether SABR added to pembrolizumab improves time to development of new metastatic lesions
Measured: 5.2 years after first patient in
Time to progression in oligometastatic lesions initially present at enrolment
To assess whether SABR added to pembrolizumab improves time to progression in oligometastatic lesions initially present at enrolment
Measured: 5.2 years after first patient in
Adverse events according to CTCAE version 5.0
To evaluate the safety and tolerability according to CTCAE v5.0 of SABR combined with pembrolizumab
Measured: 5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaire
Measured: 5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC QLQ-HN43 questionnaire
Measured: 5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC IL-198 questionnaire
Measured: 5.2 years after first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2023
- Study start23 May 2025
- Primary completion15 Jul 2027 (estimated)
- Study completion30 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oligometastatic Squamous Cell Carcinoma of the Head and NeckStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Swiss Cancer Institute, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Panagiotis Belermpas, MD, Study chair, University of ZurichJean-Pascal Machiels, MD, Study chair, Clinicque Universitarie Saint Luc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05815927
- Sponsor's protocol ID
- EORTC-2014-HNCG
- Other IDs
- 2023-504478-39-00, 2023
- Acronym
- PROLoNg
- Status last verified
- May 2026
- First submitted
- 13 Mar 2023
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab and Radiotherapy for OLigometastatic Squamous Cell Carcinoma of the Head and Neck: a Randomized Phase III Study
- ClinicalTrials.gov ID
- NCT05815927
- Acronym / sponsor ID
- PROLoNg / EORTC-2014-HNCG
- Keywords
- Pembrolizumab, Stereotactic ablative radiotherapy, oligometastatic HNSCC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Swiss Cancer Institute, Merck Sharp & Dohme LLC
- Study start
- 23 May 2025 (actual)
- Primary completion
- 15 Jul 2027 (estimated)
- Study completion
- 30 Mar 2030 (estimated)
- First posted
- 18 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized open-label multicentre phase III superiority study of the effect of adding SABR to the standard of care treatment pembrolizumab on progression free survival in patients with oligometastases of a squamous cell carcinoma of the head and neck (SCCHN), histological confirmation of the primary disease at first diagnosis, and PD-L1 CPS ≥1. After eligibility check and signing informed consent, all patients will be prospectively enrolled in a 1:1 ratio between current standard of care treatment (pembrolizumab, Arm 1) vs. SABR + standard of care treatment (Arm 2) to oligometastases.
Any radical treatment to the synchronous primary/ recurrent primary tumor and/or involved cervical nodes (surgery or radiotherapy), as decided by the local tumor board/ treating physicians, should be completed prior to enrolment.Surgical removal of metastases is allowed for diagnostic purposes or for brain metastases, as long as these metastases count toward the total number of 5 and at least one metastasis is left for treatment with SABR. Such surgical procedures should be performed prior to enrolment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 : Standard of Care | Active comparator | Drug: PembrolizumabPembrolizumab at a dose of 400mg every 6-weeks (Q6W) for a duration of 2 years (i.e 17 cycles) as per Standard of Care treatment of oligometastatic HNSCC disease. Palliative radiotherapy to oligometastatic disease is allowed if necessary as per standard of care to relieve symptomatic disease and prevent complications. Recommended dose regimens are 1x 8 Gy, 5x 4 Gy and 10x 3 Gy. Planning technique and target volume definition should be according to institutional standards.No ablative-stereotactic dose and no boost techniques are allowed with the exception of CNS-metastases treatment. |
| Arm 2 : Standard of Care + stereotattic ablative radiation (SABR) | Experimental | Drug: Pembrolizumab, Radiation: stereotattic ablation radiotherapy (SABR)The Experiemnt Arm consists of pembrolizumab at a dose of 400mg every 6-weeks (Q6W) for a duration of 2 years (i.e 17 cycles) as per Standard of Care treatment of oligometastatic HNSCC disease in combination with SABR. For each oligometastatic lesion treatment, specific SABR fractions and targeted dose(Gy) should be used depending on the location of the lesion. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments have to be completed within 10 working days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPembrolizumab: 400mg Q6W up to 2 years (i.e 17 cycles). | Drug | Arm 1 : Standard of Care, Arm 2 : Standard of Care + stereotattic ablative radiation (SABR) |
| stereotattic ablation radiotherapy (SABR)Also: SBRTTotal dose and number of fractions will depend on the site of the disease. Three-fraction regimens will deliver a fraction every second day, and five-fraction regimens are delivered daily. All treatments have to be completed within 10 working days. | Radiation | Arm 2 : Standard of Care + stereotattic ablative radiation (SABR) |
Primary outcome
Progression-free survival by RECIST 1.1
Time frame: 2.6 years after first patient in
To assess whether SABR added to pembrolizumab improves progression-free survival in patients with HNSCC disease, PD-L1 CPS ≥1 and 1-5 metastatic lesions, as compared to pembrolizumab alone.
9 secondary outcomes
Overall survival
Time frame: 5.2 years after first patient in
Disease-specific survival
Time frame: 5.2 years after first patient in
Time to disease progression
Time frame: 5.2 years after first patient in
Time to development of new metastatic lesions
Time frame: 5.2 years after first patient in
Time to progression in oligometastatic lesions initially present at enrolment
Time frame: 5.2 years after first patient in
Adverse events according to CTCAE version 5.0
Time frame: 5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaire
Time frame: 5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC QLQ-HN43 questionnaire
Time frame: 5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC IL-198 questionnaire
Time frame: 5.2 years after first patient in
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Panagiotis Belermpas, MD study chair
University of Zurich
Jean-Pascal Machiels, MD study chair
Clinicque Universitarie Saint Luc
30 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab and stereotattic ablation radiotherapy (SABR) in people with Oligometastatic Squamous Cell Carcinoma of the Head and Neck, run by European Organisation for Research and Treatment of Cancer - EORTC at 30 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain, Italy, Switzerland, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact EORTC HQ (+32 2 774 16 11, eortc@eortc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival by RECIST 1.1 (time frame: 2.6 years after first patient in). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.