Pembrolizumab and Radiotherapy for Oligometastatic Head and Neck Cancer

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC

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 volunteers

Qualifiers

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

Design model

Parallel

Treatments tested in this trial

  • Pembrolizumab

    Drug

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

  • 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.

Treatment groups

200 Participants
are divided into 2 treatment groups
Group A: Arm 1 : Standard of CareActive comparator 1 intervention
Group B: Arm 2 : Standard of Care + stereotattic ablative radiation (SABR)Experimental treatment 2 interventions

Trial outcomes

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.

Time frame
2.6 years after first patient in

Secondary outcomes

1

Overall survival

To assess whether SABR added to pembrolizumab improves OS

Time frame
5.2 years after first patient in
2

Disease-specific survival

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

Time frame
5.2 years after first patient in
3

Time to disease progression

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

Time frame
5.2 years after first patient in
4

Time to development of new metastatic lesions

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

Time frame
5.2 years after first patient in

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

European Organisation for Research and Treatment of Cancer - EORTC

Lead sponsor

Swiss Cancer Institute

Collaborator

Merck Sharp & Dohme LLC

Collaborator