About this trial
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
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Parallel
Treatments tested in this trial
Pembrolizumab
DrugPembrolizumab: 400mg Q6W up to 2 years (i.e 17 cycles).
stereotattic ablation radiotherapy (SABR)
RadiationTotal 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.
Treatment groups
Trial outcomes
Primary outcomes
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.
Secondary outcomes
Overall survival
To assess whether SABR added to pembrolizumab improves OS
Disease-specific survival
To assess whether SABR added to pembrolizumab improves disease-specific survival
Time to disease progression
To assess whether SABR added to pembrolizumab improves time to disease progression
Time to development of new metastatic lesions
To assess whether SABR added to pembrolizumab improves time to development of new metastatic lesions
Sponsors and contacts
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European Organisation for Research and Treatment of Cancer - EORTC
Lead sponsor
Swiss Cancer Institute
Collaborator
Merck Sharp & Dohme LLC
Collaborator