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Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer

Phase 3
Not yet recruiting
Conditions
Oligometastatic Squamous Cell Carcinoma of the Head and Neck
Interventions
Radiation: stereotattic ablation radiotherapy (SABR)
Registration Number
NCT05815927
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
200
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2 : Standard of Care + stereotattic ablative radiation (SABR)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.
Arm 1 : Standard of CarePembrolizumabPembrolizumab 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)PembrolizumabThe 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.
Primary Outcome Measures
NameTimeMethod
Progression-free survival by RECIST 1.12.6 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.

Secondary Outcome Measures
NameTimeMethod
Time to disease progression5.2 years after first patient in

To assess whether SABR added to pembrolizumab improves time to disease progression

Time to development of new metastatic lesions5.2 years after first patient in

To assess whether SABR added to pembrolizumab improves time to development of new metastatic lesions

Disease-specific survival5.2 years after first patient in

To assess whether SABR added to pembrolizumab improves disease-specific survival

Time to progression in oligometastatic lesions initially present at enrolment5.2 years after first patient in

To assess whether SABR added to pembrolizumab improves time to progression in oligometastatic lesions initially present at enrolment

Overall survival5.2 years after first patient in

To assess whether SABR added to pembrolizumab improves OS

Adverse events according to CTCAE version 5.05.2 years after first patient in

To evaluate the safety and tolerability according to CTCAE v5.0 of SABR combined with pembrolizumab

Health-related quality of life evaluated using self-administered EORTC QLQ-HN43 questionnaire5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC IL-198 questionnaire5.2 years after first patient in
Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaire5.2 years after first patient in

Trial Locations

Locations (26)

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

🇮🇹

Ravenna, Italy

Azienda ospedaliero Univ Policlinico Umberto I

🇮🇹

Rome, Italy

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

🇪🇸

Barcelona, Spain

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

🇪🇸

Barcelona, Spain

Inselspital - Inselspital

🇨🇭

Bern, Switzerland

Kantonsspital Graubuenden

🇨🇭

Chur, Switzerland

Cliniques Universitaires Saint-Luc

🇧🇪

Brussels, Belgium

AZ Groeninge Kortrijk - Campus Kennedylaan

🇧🇪

Kortrijk, Belgium

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

🇧🇪

Namur, Belgium

VITAZ St Niklaas - VITAZ- Oncology

🇧🇪

Sint Niklaas, Belgium

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

🇧🇪

Wilrijk, Belgium

IRCCS--Ospedale Bellaria-Bologna

🇮🇹

Bologna, Italy

AUSL - Ospedale Infermi

🇮🇹

Faenza, Italy

Univ. of Florence -Azienda Ospedaliero-Universitaria Careggi

🇮🇹

Florence, Italy

AUSL -Ospedale Umberto I

🇮🇹

Lugo, Italy

Istituto Clinico Humanitas

🇮🇹

Milan, Italy

IRCCS - Fondazione Istituto Nazionale dei Tumori

🇮🇹

Milan, Italy

Azienda Sanitaria Locale Napoli 1 Centro

🇮🇹

Napoli, Italy

Hospital Universitario de Gran Canaria Doctor Negrin

🇪🇸

Las Palmas De Gran Canaria, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitario San Carlos

🇪🇸

Madrid, Spain

Kantonsspital Aarau

🇨🇭

Aarau, Switzerland

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

🇨🇭

Bellinzona, Switzerland

Luzerner Kantonsspital

🇨🇭

Luzern, Switzerland

Kantonsspital Winterthur

🇨🇭

Winterthur, Switzerland

UniversitaetsSpital Zurich

🇨🇭

Zürich, Switzerland

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