Trial evaluating the tolerance and safety of durvalumab - radiotherapy combination for treatment of cancers of the head and neck

Phase 1

Conditions: ntreated squamous cell carcinoma of the head and neck
MedDRA version: 26.1Level: PTClassification code: 10060121Term: Squamous cell carcinoma of head and neck Class: 100000004864
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2024-513977-31-00

Lead Sponsor: Groupe Oncologie Radiotherapie Tete Cou

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 61

Inclusion Criteria

Age > 18 years with no upper limit, Performance Status ECOG 0-2, Squamous cell carcinoma, previously untreated, T1-T4 with clinical status N0-N1, N2a or N2b non palpable, with only homolateral lymph node in radiological examinations., Patient with at least one of these fragility criteria : o Status ECOG 1 with multiple comorbidities, at least 2 pathologies with grade = 2 (renal and/or cardiac and/or vascular and/or hepatic, and/or neurologic, and/or pulmonary) o Status ECOG = 2 o Age = 70 , judged unfit with oncogeriatric evaluation by EGE (ELAN Geriatric Evaluation) test or unable to receive cisplatine or Carboplatine- 5FU (at least one criteria listed below*) * Criteria for determining if a patient is unfit for receiving cisplatine or carbo-5FU : Calculated creatinine clearance = 60 mL/min as determined by the modified. method of Cockcroft and Gault or glomerular filtration rate = 60 mL/min/1.73m² (CKD-EPI method recommended) Haemoglobin < 10 g/dL, aspartate (AST) and alanine transaminase (ALT) more than 2 times the upper limit of the normal range (ULN), serum albumin =35 g/L, Absolute neutrophil count = 1 500/µL, platelets = 100 000/µL or total bilirubin = 1.5 mg/dL Cardiac function not compatible with hyperhydration or significant heart disease Weight loss > 15% in 2 months, Oral cavity, oropharynx, hypopharynx or larynx, Documentation of p16 disease (HPV status for oropharyngeal tumor), Glomerular filtration rate (GFR) >40 mL/min/1.73m2 (CKD-EPI method recommended) or Calculated creatinine clearance CL>40 mL/min by the Cockcroft- Gault formula

Exclusion Criteria

Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers, Metastatic disease, Any prior or current treatment for invasive head and neck cancer, Any unresolved toxicity NCI CTCAE v5.0 Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. a. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator, Body weight = 30 kg and/or weight loss of = 15% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing), Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis, Active autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]), Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the regional (cervical) control of durvalumab treatment combined with radiotherapy to the tumor site including the primary tumor and the invaded cervical lymph nodes and the 1st lymph node level, without prophylactic irradiation of the N0 regions in patients with T1-T4 N0-N2b squamous cell carcinoma of the head and neck.;Secondary Objective: Tolerance and safety of durvalumab combined with RT, as early and late treatmentrelated adverse events of grade = 2 according to the NCI CTCAE v5.0, Local control (site of the primary tumor), Locoregional (cervical) control, Final cervical control including salvage surgery and/or RT in case of lymph node relapse, Distant metastases control, Overall survival, Objective response rate, Progression-free survival, Health-related quality of life, Immune or biological markers potentially associated with patient outcome;Primary end point(s): Regional (neck) nodal control rate at 1 year

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Early and late adverse events of grade = 2, according to the CTCAE V5.0;Secondary end point(s):Local control at the primary site;Secondary end point(s):Locoregional nodal + primary site control rate;Secondary end point(s):Distant metastases control rate;Secondary end point(s):Ultimate regional control including salvage surgery and/or salvage RT);Secondary end point(s):Overall survival;Secondary end point(s):Objective Response Rate;Secondary end point(s):Progression-free survival;Secondary end point(s):QLQ C30 and QLQ-H&N35 scores at baseline, 3, 12 and 24 months post RT

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