A phase III study on using immunotherapy and radiotherapy to treat limited spread of Head and Neck Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 May 2025 → ongoing

Decision date (initial)

2024-11-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MSD Oncology Investigator Studies Program · EORTC Cancer Research Fund · Foundation Against Cancer · MSD Merck Sharp & Dohme AG · Asociación Española contra el Cáncer

External identifiers

EU CT number

2023-504478-39-00

ClinicalTrials.gov

NCT05815927

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Efficacy, Safety

To assess whether SABR added to pembrolizumab improves progression-free survival in patients with squamous cell carcinoma of the head and neck, PD-L1 CPS ≥1 and 1-5 metastatic lesions (“oligometastatic disease”), as compared to pembrolizumab alone.

Secondary objectives 4

1. To assess whether SABR added to pembrolizumab improves: • Overall survival (OS) • Disease-specific survival • Time to disease progression • Time to development of new metastatic lesions • Time to progression in oligometastatic lesions initially present at enrolment
2. To evaluate the safety and tolerability according to CTCAE v5.0 of SABR combined with pembrolizumab
3. To establish the patient-reported tolerability profile of both treatment arms
4. To compare the patient-reported benefit between the two treatment arms

Conditions and MedDRA coding

Squamous cell carcinoma of head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Male/female participants who are at least 18 years of age on the day of signing informed consent
2. Histologically confirmed squamous cell carcinoma of the head and neck 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
3. 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 c/rcN1-N3 present)
4. Amenable to first-line systemic treatment for R/M SCCHN
5. For patients with oropharyngeal cancer: HPV status using p16 IHC evaluated locally
6. PD-L1 CPS of at least 1 as evaluated locally
7. Staging not older than 12 weeks before enrolment
8. All the 1-5 metastases must be amenable to SABR
9. Eligible for treatment with pembrolizumab
10. Measurable disease based on RECIST 1.1
11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
12. Recovered from the treatment-related toxicities, such as from previous radiotherapy, systemic treatment or surgery, that otherwise would preclude the treatment with pembrolizumab or SABR, and not requiring corticosteroids for managing treatment-related side effects such as oedema, pneumonitis, pain
13. Adequate Organ Function Laboratory Values
14. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to enrolment and, the test must be repeated within 72 hours prior to the first dose of study treatment
15. Patients of childbearing / reproductive potential should use highly effective birth control measures, as defined by the investigator, during the study treatment period and for at least 4 months after the last dose of treatment. Male participant must refrain from donating sperm during this period. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. For women such methods include: • Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) • Intrauterine device (IUD) • Intrauterine hormone-releasing system (IUS) • Bilateral tubal occlusion • Vasectomized partner • Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
16. Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment
17. Before patient registration/enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion criteria 15

1. Nasopharynx, sino-nasal, and salivary gland cancers are excluded
2. In-field progression in < 6 months after curative intended locoregional irradiation of the head and neck
3. 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 (e.g., rib, scapula, pelvis) and no inner organ is affected
4. Brain metastases only
5. Non resected brain metastases > 4cm diameter
6. 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.
7. Received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of inactivated vaccines is allowed
8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 12 weeks prior to the first dose of study intervention
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
10. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer) that have undergone potentially curative therapy are not excluded, neither patient treated with adjuvant hormonal therapy (e.g., breast cancer)
11. 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 (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention, can participate
12. Known contraindications to both PET-CT and CT scan or, in the sites with only one of the two methods available, known contraindication to the available method (either PET CT or CT scan)
13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
14. Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
15. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before enrolment in the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival by RECIST 1.1, as assessed by the local investigator

Secondary endpoints 8

1. Overall survival
2. Disease-specific survival
3. Time to disease progression
4. Time to development of new metastatic lesions
5. Time to progression in oligometastatic lesions initially present at enrolment
6. Adverse events according to CTCAE version 5.0
7. Patient reported tolerability: dyspnoea, pain, insomnia, fatigue, appetite loss, nausea, constipation, diarrhoea, anxiety, coughing, dry mouth, neurological problems, trismus, problems with senses, problems with shoulder, skin problems, swallowing, swelling in neck, problems with speech, problems with teeth and weight loss scales as measured by the QLQ-C15-PAL and EORTC IL243 questionnaires
8. Patient reported benefit: physical functioning and burden of illness scales as measured by the QLQ-C15-PAL and EORTC IL243

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83/11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stéphanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 3

Locations

3 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications