Study comparing radiotherapy combined with cetuximab + Xevinapant (study drug) with radiotherapy combined with cetuximab + placebo in patients with head and neck cancer.

Trial details

Who runs it

Groupe Oncologie Radiotherapie Tete Cou

Trial code

EU 2022-502584-38-00

Record updated

2024. február 14.

Original description

To demonstrate improvement in PFS evaluated by an independent review committee (IRC) with xevinapant-cetuximab-RT compared to placebo-cetuximab-RTRead full original descriptionShow less

A double-blind randomized, Phase III study of radiotherapy combined with cetuXimab + Xevinapant compared to radiotherapy combined with cetuximab (Standard of care) + placebo in patients with Locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN), unfit for high-dose cisplatin (XXL study)

To demonstrate improvement in PFS evaluated by an independent review committee (IRC) with xevinapant-cetuximab-RT compared to placebo-cetuximab-RT

Inclusion: Male or Female ≥ 18 years (or based on the country legal age limit for adults on day of signing the Informed Consent Form, ICF) and < 80 years; ECOG PS 0-1; Histologically confirmed diagnosis in previously untreated LA-SCCHN participant (Stage III, IVA or IVB according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed.) of at least one of the following sites: oral cavity, hypopharynx and larynx. OPC participants are also eligible but their primary tumor must be: • HPV-negative (Stage III, IVA or IVB according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed.) or • HPV-positive and smokers > 20 PY and must have according to the American Joint Committee on Cancer [AJCC]/TNM Staging System, 8th Ed: o T3 N1-3 o T4 and any N; Able to swallow liquids or have an adequately functioning feeding tube, gastrostomy or jejunostomy placed; Patients must be ineligible to receive high-dose cisplatin defined as ≥ 200 mg/m² (projected total cumulative dose throughout the course of the RT). Ineligibility is defined as at least one of the following criteria: • eGFR < 60 mL/min /1.73 m² (using the CKD-EPI creatinine formula) • History of hearing loss, defined as either: i. Existing need of a hearing aid and/or ii. Clinically relevant hearing loss by clinical assessment including tinnitus ≥ Grade 2. Note: In case of doubt, an audiogram should be requested to guide the Investigator • Peripheral neuropathy ≥ Grade 2 • Cardiac function not compatible with hyperhydration • If > 70 years, unfit according to G8 questionnaire (Score ≤ 14); Adequate hematologic, renal and hepatic function as indicated by (using CTCAE v5.0): • Absolute neutrophil count ≥ 1500 /mm3 • Platelets ≥ 100 000 /mm3 • Hemoglobin ≥ 9.0 g/dL (blood transfusions during Screening are not permitted) • White blood cells ≥ 3 000/mm3 • AST and ALT ≤ 3 × ULN • eGFR ≥ 30 mL/min /1.73 m² (using the CKD-EPI creatinine formula) • Total bilirubin ≤ 1.5 × ULN (up to 2.0 × ULN is allowed if the direct bilirubin level is normal, and the elevation is limited to indirect bilirubin); The Investigator confirms that the participant agrees to use appropriate contraception and barriers methods, if applicable; Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the inform consent form and this protocol.

Exclusion: Active gastrointestinal bleeding, or any other uncontrolled bleeding requiring more than 2 red blood cell transfusions or 4 units of packed red blood cells within 4 weeks prior to randomization; Active uncontrolled inflammatory disease (including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, severe extensive psoriasis, and other autoimmune diseases) requiring ongoing treatment with anti-TNF medication; Any condition, including any uncontrolled disease state other than SCCHN that in the Investigator’s opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation; Symptomatic pulmonary disease requiring continuous or intermittent oxygen supply; History of another malignancy within the last 3 years prior to randomization, with the exception of completely resected non-melanoma cell skin cancer outside the head and neck area or completely resected stage I breast cancer, or completely resected in-situ non-muscular invasive bladder, cervix and/or uterine carcinomas; Metastatic disease (according to AJCC/TNM, 8th ed.); Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery that may limit oral absorption; Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following; Hypertension uncontrolled by medication (i.e. systolic blood pressure > 150 mmHg and diastolic blood pressure > 90 mmHg); Documented weight loss of > 10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin < 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization; Non compensated or symptomatic liver cirrhosis (Child-Pugh score: B or C); Primary tumor of nasopharyngeal, paranasal sinuses, salivary, thyroid or parathyroid gland, skin or unknown primary site.

EU CTIS 2022-502584-38-00