A Phase II Study of TPEx (Taxotere-platinum-cetuximab) Followed by a Maintenance With Avelumab and Cetuximab in First Line Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (TATIANA)
The main objective of this research is to increase the life expectancy of patients with advanced mouth and throat cancer, by adding avelumab to the standard TPEx treatment. All participants in this research will receive the same treatment which will take place in two phases: * 1st phase chemotherapy + immunotherapy: standard reference treatment (Docetaxel + cisplatin or carboplatin + cetuximab) * 2nd phase immunotherapy: cetuximab combined with avelumab which is the treatment under study.
• Adult men and women ≥ 18 years and \< 75 years.
• Histologically confirmed recurrent and/or metastatic SCCHN (oral cavity, pharynx, larynx), not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy); squamous cell carcinoma of unknown primary if HPV positive.
• Detection of PD-L1 protein expression in formalin-fixed, paraffin-embedded (FFPE) SCCHN tissue samples determined by Combined Positive Score (CPS) ≥1 using local IHC assay.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Patients without contra indication to TPEx (either with cisplatin or carboplatin), to docetaxel, cetuximab and to immunotherapy (avelumab).Investigators must refer to the last updated version of Summary of product Characteristics (SPC) of the products.
• Documentation of p16 status as surrogate of human papillomavirus (HPV) status of tumor for SCC of the oropharynx.
• Measurable disease by CT or MRI per RECIST 1.1 criteria.
• In case of radiotherapy given without systemic treatment, prior curative radiation therapy must have been completed at least 4 weeks before TPEx administration and/or prior palliative radiotherapy must have been completed at least 2 weeks before TPEx administration.
• Screening laboratory values must meet the following criteria (using NCI-CTCAE v5) and should be obtained within 14 days prior to eligibility check:
∙ WBC \> 2000/μL
‣ Polynuclear neutrophils \>1.5 x 109/L
‣ Platelets \> 100 x 109/L
‣ Hemoglobin \> 9.0 g/mL
‣ ALAT/ASAT\< 3.0 x ULN in the absence of liver metastases or \< 5x ULN in the presence of liver metastases
‣ Bilirubin \< 1.5 x ULN (except Gilbert Syndrome: \< 3.0 mg/dL)
‣ Creatinine clearance \> 60 mL/min (measured or calculated by preferably Cockcroft and Gault formula) for cisplatin administration and creatinine clearance between ≥ 40 mL/min and ≤ 60 mL/min (measured or calculated by preferably Cockcroft and Gault formula) for carboplatin administration.
⁃ Calcium levels must be normalized and maintained within normal limits for study entry. Medical management of calcium levels is permitted. Note: Normal calcium levels may be based on ionized calcium or adjusted for albumin.
⁃ Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically non-significant by the Investigator and/or stable on supportive therapy.
⁃ Women of childbearing potential must have a negative serum or urine pregnancy test at the eligibility check. The pregnancy test must be done within 72 hours before eligibility check.
⁃ Both men and women (of childbearing potential) who are sexually active must agree to use highly effective contraceptive method(s) from ICF signature to at least 7 months post-treatment for women and 4 months post-treatment for men.