PEMBROLIZUMAB for Squamous cell carcinoma of head and neck

Inclusion criteria

• {"criterion_text":"- Male/female participants who are at least 18 years of age on the day of signing informed consent\n- Measurable disease based on RECIST 1.1\n- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1\n- 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\n- Adequate Organ Function Laboratory Values\n- 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\n- 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)\n- 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\n- Before patient registration/enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations\n- 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\n- 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)\n- Amenable to first-line systemic treatment for R/M SCCHN\n- For patients with oropharyngeal cancer: HPV status using p16 IHC evaluated locally\n- PD-L1 CPS of at least 1 as evaluated locally\n- Staging not older than 12 weeks before enrolment\n- All the 1-5 metastases must be amenable to SABR\n- Eligible for treatment with pembrolizumab"}

Exclusion criteria

• {"criterion_text":"- Nasopharynx, sino-nasal, and salivary gland cancers are excluded\n- 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)\n- 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\n- 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)\n- 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\n- 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\n- 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\n- In-field progression in < 6 months after curative intended locoregional irradiation of the head and neck\n- 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\n- Brain metastases only\n- Non resected brain metastases > 4cm diameter\n- 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.\n- 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\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival by RECIST 1.1, as assessed by the local investigator","definition_or_measurement_approach":"Progression-free survival measured by RECIST 1.1 assessed by the local investigator"}

Secondary endpoints

• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease-specific survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to disease progression","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to development of new metastatic lesions","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to progression in oligometastatic lesions initially present at enrolment","definition_or_measurement_approach":""}
• {"endpoint_text":"- Adverse events according to CTCAE version 5.0","definition_or_measurement_approach":"Adverse events graded and reported according to CTCAE v5.0"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured by the QLQ-C15-PAL and EORTC IL243 patient-reported questionnaires"}
• {"endpoint_text":"- Patient reported benefit: physical functioning and burden of illness scales as measured by the QLQ-C15-PAL and EORTC IL243","definition_or_measurement_approach":"Measured by the QLQ-C15-PAL and EORTC IL243 patient-reported questionnaires"}

Belgium

Earliest CTIS Part Ii Submission Date

09-10-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

34

Number Of Sites

6

Number Of Participants

58

Italy

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

14-11-2024

Processing Time Days

29

Number Of Sites

8

Number Of Participants

76

Spain

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

18-11-2024

Processing Time Days

39

Number Of Sites

8

Number Of Participants

26

Primary sponsor

Full Name

European Organisation For Research And Treatment Of Cancer

Organisation Type

Patient organisation/association

Country Of Registered Address

Belgium

Third parties

• {"country":"Switzerland","full_name":"Swiss Cancer Institute","duties_or_roles":"Functioning as legal representative, regulatory activities and site management","organisation_type":"Patient organisation/association"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"Drug distribution","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Vall D Hebron Institute Of Oncology","duties_or_roles":"Receival of human biological material","organisation_type":"Laboratory/Research/Testing facility"}