Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma
- Conditions
- Interventions
- Registration Number
- NCT06706401
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
The aim of this study is to investigate the effect of ATRA (Vesanoid) and the effect of tailored radiotherapy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx.
- Detailed Description
Following validation of eligibility criteria, patients will be randomised (1:1:1:1) to receive:
* Arm A: Standard radiotherapy then follow-up
* Arm B: Tailored radiotherapy and ATRA (Vesanoid)
* Arm C: Standard radiotherapy and ATRA (Vesanoid)
* Arm D: Tailored radiotherapy then follow-up
...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 460
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Standard radiotherapy Standard radiotherapy Patient will receive 6 to 8 weeks of standard (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Standard radiotherapy Cisplatin Patient will receive 6 to 8 weeks of standard (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Standard radiotherapy Cetuximab Patient will receive 6 to 8 weeks of standard (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Tailored radiotherapy and ATRA (Vesanoid) Vesanoid ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). Then, patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy. In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Tailored radiotherapy and ATRA (Vesanoid) Tailored radiotherapy ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). Then, patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy. In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Tailored radiotherapy and ATRA (Vesanoid) Cisplatin ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). Then, patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy. In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Tailored radiotherapy and ATRA (Vesanoid) Cetuximab ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). Then, patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy. In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Standard radiotherapy and ATRA (Vesanoid) Vesanoid ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments).Then, patient will receive 6 to 8 weeks of standard (chemo)radiotherapy. Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Standard radiotherapy and ATRA (Vesanoid) Standard radiotherapy ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments).Then, patient will receive 6 to 8 weeks of standard (chemo)radiotherapy. Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Standard radiotherapy and ATRA (Vesanoid) Cisplatin ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments).Then, patient will receive 6 to 8 weeks of standard (chemo)radiotherapy. Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Standard radiotherapy and ATRA (Vesanoid) Cetuximab ATRA will be administered per os 1 week before the start of (chemo)radiotherapy (daily administration for 3 days). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments).Then, patient will receive 6 to 8 weeks of standard (chemo)radiotherapy. Subsequently, ATRA will be administered per os for 3 days every 3 weeks for a total of 4 courses starting 2 to 3 weeks after the end of (chemo)radiotherapy. Finally, the patient will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). Tailored radiotherapy Tailored radiotherapy Patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Tailored radiotherapy Cisplatin Patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments). Tailored radiotherapy Cetuximab Patient will receive 6 to 8 weeks of tailored (chemo)radiotherapy then will be followed until document progression disease, death, withdrawal of consent or end of trial (whichever occurs first). In addition of radiotherapy, patient will receive cisplatin or cetuximab (standard of care treatments).
- Primary Outcome Measures
Name Time Method Event Free Survival (EFS) At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years Event free survival (EFS) is defined as the time from randomisation to apparition of a documented relapse either local or regional or distant according to clinical or radiological assessment, or persistent residual disease including pathologically positive neck node, or death due to any cause.
- Secondary Outcome Measures
Name Time Method Local relapse Free Survival At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years Local relapse Free Survival (lrFS, at site of primary tumor) is defined as the delay from randomisation to first local relapse (i.e. primary site) or death. Patients without documented event will be censured at the last adequate visit or tumor evaluation.
Regional relapse Free survival At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years Regional relapse Free survival (rrFS, in the neck) is defined as the delay from randomisation to first regional relapse (i.e. neck) or death.
Metastasis Free Survival At 6, 9, 15, 21 and 27 months from randomisation then annually assessed up to 2 years Metastasis Free Survival (mFS) is the time between randomisation and apparition of first metastasis (date of metastatic diagnosis). Patients without documented event will be censured at the last tumour evaluation.
Rate of pathologically positive lymph nodes At 4 months from the completion of (chemo)-radiotherapy Rate of pathologically positive lymph nodes at neck node dissection performed at 4 months after the completion of (chemo)-radiotherapy for those patients benefiting from a neck node dissection
Event Free Survival (EFS) At 4 months from the completion of (chemo)-radiotherapy Event Free Survival (EFS) considering that pathologically positive neck node within 4 months post-randomisation will not be an event.
Overall survival Until up to 2 years follow-up of the last patient enrolled Overall survival defined as the time from randomisation to death due to any cause. Patient without documented death at the time of analysis will be censored at the date of last known contact.
Adverse events From the date of first intake of study drug until 27 months after the randomisation of the last randomised patient Incidence of any adverse events graded according to NCI-CTCAE V5.0
Patient quality of life (EORTC QLQ-C30) At randomisation, at 6, 9, 15, 21 and 27 months after randomisation and30 days after the last study treatments administration To assess the impact of the proposed combinations on patient' quality of life in the target population (EORTC QLQ-C30)
Patient quality of life (EQ5-DL) At randomisation, at 6, 9, 15, 21 and 27 months after randomisation and30 days after the last study treatments administration To assess the impact of the proposed combinations on patient' quality of life in the target population (EQ5-DL)
Patient quality of life (EORTC QLQ-H&N43) At randomisation, at 6, 9, 15, 21 and 27 months after randomisation and30 days after the last study treatments administration To assess the impact of the proposed combinations on patient' quality of life in the target population (EORTC QLQ-H\&N43)
Health economic analysis From the first patient enrolled to 2 years after treatment discontinuation of the last patient enrolled To perform an economic analysis of the use of a tailored-RT with or without ATRA (Vesanoid). A cost-effectiveness methodology will be implemented, which involves computing costs and efficacy for each of the four treatment arms.
Immunomonitoring Cycle 1 Day 1 pre-dose of Vesanoid, Day 1 of radiotherapy and end of radiotherapy (8 to 10 weeks after randomisation) To study the impact of treatment on lymphocytes number and function, including by assessing immunosenescence induction and to study blood biomarkers predictive of response/toxicity following treatment
Trial Locations
- Locations (1)
Centre Léon Bérard
🇫🇷Lyon, France