Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer

NCT05815927 | Recruiting Phase 3 DMC

• 2 other identifiers: EORTC-2014-HNCG2023-504478-39-00
• Study Type: interventional
• Target: 200
• Locations: 4 countries
• Sites: 30

Brief 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 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.

Conditions

Oligometastatic Squamous Cell Carcinoma of the Head and Neck

Keywords

Pembrolizumab; Stereotactic ablative radiotherapy; oligometastatic HNSCC

Outcome Measures

Primary Outcomes (1)

• 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.

  2.6 years after first patient in

Secondary Outcomes (9)

• Overall survival

  5.2 years after first patient in

• Disease-specific survival

  5.2 years after first patient in

• Time to disease progression

  5.2 years after first patient in

• Time to development of new metastatic lesions

  5.2 years after first patient in

• Time to progression in oligometastatic lesions initially present at enrolment

  5.2 years after first patient in

Study Arms (2)

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.

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.

Drug: Pembrolizumab; Radiation: stereotattic ablation radiotherapy (SABR)

Interventions

Pembrolizumab DRUG

Pembrolizumab: 400mg Q6W up to 2 years (i.e 17 cycles).

Arm 1 : Standard of Care; Arm 2 : Standard of Care + stereotattic ablative radiation (SABR)

stereotattic ablation radiotherapy (SABR) RADIATION

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.

Also known as: SBRT

Arm 2 : Standard of Care + stereotattic ablative radiation (SABR)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Swiss Cancer Institute: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (30)

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

CHU Helora Pole Hospitalier Jolimont - Hopital Jolimont

Haine-Saint-Paul, 7100, Belgium

NOT YET RECRUITING

AZ Groeninge Kortrijk - Campus Kennedylaan

Kortrijk, 8500, Belgium

RECRUITING

CHU-UCL Namur - CHU Site Sainte-Elisabeth-UCL Namur

Namur, 5000, Belgium

RECRUITING

VITAZ St Niklaas - VITAZ- Oncology

Sint-Niklaas, 9100, Belgium

RECRUITING

Ziekenhuis aan de Stroom (ZAS) - ZAS Augustinus (previous GZA)

Wilrijk, 2610, Belgium

RECRUITING

IRCCS--Ospedale Bellaria-Bologna

Bologna, 40139, Italy

NOT YET RECRUITING

Azienda Ospedaliera Santa Croce E Carle

Cuneo, 12100, Italy

NOT YET RECRUITING

Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

NOT YET RECRUITING

Istituto Clinico Humanitas

Milan, 20089, Italy

RECRUITING

IRCCS - Fondazione Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Azienda Sanitaria Locale Napoli 1 Centro

Naples, 80147, Italy

NOT YET RECRUITING

AUSL Romagna - AUSL Della Romagna -Ospedale Santa Maria delle Croci

Ravenna, 48121, Italy

NOT YET RECRUITING

Azienda ospedaliero Univ Policlinico Umberto I

Rome, 00161, Italy

NOT YET RECRUITING

Institut Català d'Oncologia - Hospital Duran i Reynals

Badalona, 08916, Spain

NOT YET RECRUITING

Hospital Universitario De Cruces

Barakaldo, 48903, Spain

NOT YET RECRUITING

Hospital Universitari Vall d'Hebron -Vall d'Hebron Institut Oncologia

Barcelona, 08035, Spain

RECRUITING

ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)

Barcelona, 08908, Spain

RECRUITING

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

NOT YET RECRUITING

Hospital Universitario Virgen De La Victoria

Málaga, 29010, Spain

NOT YET RECRUITING

Kantonsspital Aarau

Aarau, 5001, Switzerland

NOT YET RECRUITING

Oncology Institute of Southern Switzerland (IOSI) - Oncology Institute of Southern Switzerland - Ospedale San Giovanni

Bellinzona, 6500, Switzerland

NOT YET RECRUITING

Inselspital - Inselspital

Bern, 3010, Switzerland

RECRUITING

Kantonsspital Graubuenden

Chur, 7000, Switzerland

NOT YET RECRUITING

Luzerner Kantonsspital

Lucerne, 6004, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

NOT YET RECRUITING

UniversitaetsSpital Zurich

Zurich, 8901, Switzerland

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Panagiotis Belermpas, MD

  University of Zurich

  STUDY CHAIR

• Jean-Pascal Machiels, MD

  Clinicque Universitarie Saint Luc

  STUDY CHAIR

Central Study Contacts

EORTC HQ

CONTACT

+32 2 774 16 11; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 18, 2023
• Study Start: May 23, 2025
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): March 30, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-05

Locations

BE (6); CH (7); IT (8); ES (9)