Clinical trial NCT05815927: Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer
Official title: Pembrolizumab and Radiotherapy for OLigometastatic Squamous Cell Carcinoma of the Head and Neck: a Randomized Phase III Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Oligometastatic Squamous Cell Carcinoma of the Head and Neck
Keywords: Pembrolizumab
Stereotactic ablative radiotherapy
oligometastatic HNSCC
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Swiss Group for Clinical Cancer Research
name: Merck Sharp & Dohme LLC
First posted: 2023-04-18
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival by RECIST 1.1
timeFrame: 2.6 years after first patient in
Secondary outcomes:
measure: Overall survival
timeFrame: 5.2 years after first patient in
measure: Disease-specific survival
timeFrame: 5.2 years after first patient in
measure: Time to disease progression
timeFrame: 5.2 years after first patient in
measure: Time to development of new metastatic lesions
timeFrame: 5.2 years after first patient in
measure: Time to progression in oligometastatic lesions initially present at enrolment
timeFrame: 5.2 years after first patient in
measure: Adverse events according to CTCAE version 5.0
timeFrame: 5.2 years after first patient in
measure: Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaire
timeFrame: 5.2 years after first patient in
measure: Health-related quality of life evaluated using self-administered EORTC QLQ-HN43 questionnaire
timeFrame: 5.2 years after first patient in
measure: Health-related quality of life evaluated using self-administered EORTC IL-198 questionnaire
timeFrame: 5.2 years after first patient in
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Kortrijk
country: Belgium
facility: AZ Groeninge Kortrijk - Campus Kennedylaan
city: Namur
country: Belgium
facility: CHU-UCL Namur - CHU Site Sainte-Elisabeth-UCL Namur
city: Sint Niklaas
country: Belgium
facility: VITAZ St Niklaas - VITAZ- Oncology
city: Wilrijk
country: Belgium
facility: Ziekenhuis aan de Stroom (ZAS) - ZAS Augustinus (previous GZA)
city: Bologna
country: Italy
facility: IRCCS--Ospedale Bellaria-Bologna
city: Faenza
country: Italy
facility: AUSL - Ospedale Infermi
city: Florence
country: Italy
facility: Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi
city: Lugo
country: Italy
facility: AUSL -Ospedale Umberto I
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Milan
country: Italy
facility: IRCCS - Fondazione Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Azienda Sanitaria Locale Napoli 1 Centro
city: Ravenna
country: Italy
facility: AUSL Romagna - AUSL Della Romagna -Ospedale Santa Maria delle Croci
city: Rome
country: Italy
facility: Azienda ospedaliero Univ Policlinico Umberto I
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron -Vall d'Hebron Institut Oncologia
city: Barcelona
country: Spain
facility: ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland (IOSI) - Oncology Institute of Southern Switzerland - Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital - Inselspital
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: UniversitaetsSpital Zurich
Study officials:
affiliation: University of Zurich
name: Panagiotis Belermpas, MD
role: STUDY_CHAIR
affiliation: Clinicque Universitarie Saint Luc
name: Jean-Pascal Machiels, MD
role: STUDY_CHAIR
References: