Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU for Locally Advanced Head and Neck Squamous Cell Carcinoma

Exclusion Criteria

• •1. Primary site of head and neck carcinoma in nasopharynx, or skin
• •2. Patients receiving other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other GnRH agonists) or other investigational agent within 30 days prior to the first dose of study drug and while on study treatment.
• •3. Patients receiving other anti-cancer non-drug therapies: radiation, or tumor embolization within 30 days prior to the first dose of study drug and while on study treatment.
• •4. No relevant toxicities (\>grade 1 CTCAE) due to prior medical treatment at time of study entry
• •5. Participation in another clinical study with an investigational product during the last 30 days
• •6. Patient with dihydropyrimidine dehydrogenase (DPD) deficiency
• •7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses. Or patient under guardianship or deprived of his liberty by a judicial or administrative decision or any condition (e.g psychiatric illness/social/familial/geographical condition) that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent
• •8. Patient with active cardiac disease or with a history of cardiac dysfunction any of the following:
• •* Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO),
• •* Mean QT interval corrected for heart rate (QTc) ≥ 470 msec calculated from 3 electrocardiograms (ECGs) performed at screening, using Fredericia's correction (QTcF),
• •* Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function,
• •* Unstable angina pectoris
• •* Uncontrolled hypertension
• •* History of documented congestive heart failure (New York Heart Association functional classification III-IV), or Uncontrolled symptomatic congestive heart failure
• •* Documented cardiomyopathy,
• •* Other cardiac arrhythmia not controlled with medication.
• •9. Other invasive malignancy within 5 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
• •10. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid
• •11. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
• •12. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
• •13. Active or prior documented inflammatory bowel disease (eg, Crohn's disease,ulcerative colitis)
• •14. History of primary immunodeficiency
• •15. History of allogenic organ transplant that requires use of immunosuppressives
• •16. Known history of previous clinical diagnosis of tuberculosis
• •17. Patients with a known HIV status
• •18. Pregnant or breast-feeding women
• •19. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• •20. History of hypersensitivity to durvalumab or any excipients or to other humanized mAbs
• •21. Any contraindication to the use of cisplatin, docetaxel and 5FU and/or known history of hypersensitivity to any of those drugs
• •22. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results