Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNICANCER
About this trial
Study to evaluate the efficacy of treatment by radiotherapy and pembrolizumab in newly diagnosed metastatic head \& neck cancers
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
Histologically confirmed squamous cell carcinoma of head and neck (oral cavity, oropharynx, hypopharynx, and larynx) including unknown primary head and neck lymph nodes with distant metastases at presentation (T1-4 N0-3 M1). Histological confirmation is required in case of a single metastatic lesion.
Eligible for treatment by pembrolizumab according to the European Marketing Authorization
Patient ≥18 years old
Disqualifiers
Symptomatic central nervous system (CNS) metastases and / or carcinomatous meningitis
History of another malignancy within 2 years prior to study inclusion, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma
Prior radiotherapy in the head and neck region
Any prior or current non-surgical treatment for invasive head and neck cancer. (except for pembrolizumab +/- chemotherapy for the current cancer for a maximum of 6 cycles). This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, chemotherapy, anti-PD-1/PD-L1 and CTLA-4, prior radiotherapy (RT), or use of any investigational agent. Loco-regional recurrent or second primary head and neck cancer after prior surgical treatment alone in the head and neck region could be eligible.
Trial design
Design model
Parallel
Treatments tested in this trial
Pembrolizumab
DrugPembrolizumab 200 mg every 3 weeks until disease progression (as confirmed according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)) or unacceptable toxicity. The treatment of pembrolizumab should not be delayed because of radiotherapy planning.
Loco-regional radiotherapy
RadiationDepending on the choice of radiotherapy timing: * Before 3 cycles of pembrolizumab with or without chemotherapy : radiotherapy could start at any time between one week after the first administration of pembrolizumab and the first day of the 3rd cycle. * After 3 cycles of pembrolizumab with or without chemotherapy : radiotherapy could start at any time after 3rd cycle (C3D1) and up to a maximum of 4 weeks after the 6th cycle of pembrolizumab. Dose/fraction of radiotherapy: 54 Gy/18 fractions (recommended schedule) or 70Gy/33-35 fractions or other curative dose/fraction schedules with shorter duration and biologically equivalent dose of at least 60Gy at the discretion of local investigators, in the head and neck region. The volume of RT will include only involved loco-regional tumor region and no prophylactic neck volume will be necessary. Other cycles of pembrolizumab will be administered during and after radiotherapy.
Chemotherapy
DrugIf the investigator decide to add chemotherapy with pembrolizumab, and depending on the radiotherapy timing: * Start of radiotherapy planned before 3rd cycle: Chemotherapy could be delayed after the end of radiotherapy and start from cycle 3 or 4 of pembrolizumab. Administration of chemotherapy can be delayed in case of non resolved grade 3 or higher toxicity from radiotherapy. * Radiotherapy planned after 3rd cycle: Chemotherapy should start at the same time of pembrolizumab. Chemotherapy will combine carboplatin AUC 5mg/mL/min or cisplatin 100mg/m² every 3 weeks with 5-FU 1000mg/m²/j during 4 days every 3 weeks for a maximum of 6 cycles
Treatment groups
102 Participants
are divided into 2 treatment groupsGroup A: Radiotherapy added to systemic treatmentExperimental treatment 3 interventions
Group B: Systemic treatmentActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Progression-free survival (PFS)
The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
Time frame
From randomization to disease progression or death, up to 3 years.Secondary outcomes
1
Overall survival (OS)
The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether the radiotherapy improves overall survival compared to standard of care.
Time frame
From randomization to death from any cause, up to 5 years.2
Quality of life questionnaire - Core 30 (QLQ-C30)
Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Time frame
At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years3
Quality of Life Questionnaire - Head & Neck Cancer Module (QLQ-H&N35)
The head \& neck cancer module is a 35-item questionnaire designed for use among a wide range of patients with head \& neck cancer, varying in disease stage and treatment modality. It includes 7 multi-item scales that assess pain (4 items), swallowing (4 items), senses (2 items), speech (3 items), social eating (4 items), social contact (5 items), and sexuality (2 items). There are also 11 single items. Using a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), patients indicate the degree to which they have experienced symptoms. For all items and scales, high scores indicate more problems.
Time frame
At baseline, 4 months, 6 months, 12 months, 18 months, 2 years, 3 years, and 4 years4
Objective response rate (ORR)
The Objective response rate is defined as the presence of a partial response (PR) or complete response (CR) observed at week 18 and at week 27 after randomization. The investigator will evaluate the objective response using RECIST v1.1.
Time frame
At 18 weeks and 27 weeksSponsors and contacts
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Source ClinicalTrials.gov