NCT06706401

Lymphocyte-Sparing And Radio-Immunotherapy in Head and Neck Carcinoma

A Multicenter, Randomised 2*2 Factorial Design Comparing Standard to Reduced-target Volume Radiotherapy With or Without All-trans Retinoic Acid (ATRA) in Patients With Lateralised Oropharyngeal, Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 460 (estimated)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 This randomised phase III clinical trial will provide the clinical proof-of-concept that unilateral irradiation for lateralized tumors and the addition of ATRA (Vesanoid) to radiotherapy in HNSCC prevents severe lymphopenia and immunosenescence and therefore, may foster a radiation-induced anticancer immune response sufficient to increase event-free survival at 2 years.

Conditions

• Oropharynx Cancer
• Larynx Cancer
• Hypopharynx Cancer
• Primary Head and Neck Tumor

Interventions

Type	Name	Description
DRUG	Vesanoid	Before (chemo)radiotherapy: D1 to D3: 150mg/m2/day, 1 week before radiotherapy. Post (chemo)radiotherapy: D1 to D3: 150mg/m2/day every 3 weeks for up to 4 cycles post (chemo)radiotherapy
RADIATION	Standard radiotherapy	70 Gy in 35 fractions of 2 Gy over 6 (6 fractions per week) or hyperfractionated RT with a median therapeutic dose of 80.5 Gy delivered in 70 fractions of 1.15 Gy over 7 weeks.
RADIATION	Tailored radiotherapy	70 Gy in 35 fractions of 2 Gy over 6 weeks (6 fractions per week) or hyperfractionated RT with a median therapeutic dose of 80.5 Gy delivered in 70 fractions of 1.15 Gy over 7 weeks.
DRUG	Cisplatin	Cisplatin is recommended for the following patients : Stage T1-T2/N2a-N2b and T3/N0-N1-N2a-N2b. concomitant chemotherapy is standard of care treatments and should be administered as per standard practice. Chemotherapy will include one of the two cisplatin regimens specified in this protocol at the discretion of the participating centers. The centers must however treat all their recruited patients with one of the two regimens chosen before site activation. Chemotherapy should start the first day of radiotherapy. Cisplatin should be infused before radiation therapy delivery. The 2 options are: • Cisplatin 100 mg/m² i.v. on day 1 and 22 of radiotherapy (when 70 Gy are delivered in 6 weeks) or on day 1, 22 and 43 (when 70 Gy are delivered in 7 weeks). or • Cisplatin 40 mg/m² i.v. on day 1, 8, 15, 22, 29, 35 of radiotherapy (when 70 Gy are delivered in 6 weeks) or on day 1, 8, 15, 22, 29, 35, 42 of radiotherapy (when 70 Gy are delivered in 7 weeks).
DRUG	Cetuximab	Cetuximab is recommended for the following patients : Stage T1-T2/N2a-N2b and T3/N0-N1-N2a-N2b. concomitant Cetuximab is standard of care treatments and should be administered as per standard practice. Cetuximab therapy will be started with an intravenous loading dose of 400 mg/m2 one week before start of RT followed by six (radiotherapy over 6 weeks) or seven (radiotherapy over 7 weeks) weekly doses of 250 mg/m2.

Timeline

• Start date: 2025-02-20
• Primary completion: 2029-01-01
• Completion: 2029-01-01
• First posted: 2024-11-26
• Last updated: 2025-11-18

Locations

7 sites across 1 country: France