Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Provision of signed written informed consent prior to any study specific procedures
Female and/or male patients aged 18 years and over
Body weight higher than 30 Kg
Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx
Provision of biological material (tumor tissue and blood), provision of signed informed consent for translational research
Patients selected for a primary surgical treatment
No prior anti-cancer treatment for head and neck cancer
Performance status ECOG 0-1
Adequate hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin ≥10g/dL
Adequate renal function: serum creatinine level 1.5 mg/dl and Glomelular Filtration Rate50 ml/min by Cockroft/Gault formula
Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase, AST (SGOT), ALT (SGPT) 5xULN
No active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
Ability to swallow tablets.
Regular follow-up feasible
Baseline evaluations performed before registration: clinical and blood evaluations no more than 1 week (7 days) prior to registration, tumour assessment (CT or MRI scan of the head and neck, chest, abdomen and pelvis at the discretion of the investigator) no more than 30 days prior to registration
Treatment initiation planned less than 1 week (7 days) after registration

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

Women <50 years of age would be considered post-menopausal if theyhave been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment
Women of childbearing potential and their partners, who are sexually active, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for at least 1-6 month (according to the treatment group) after last dose of study drug(s) (where applicable). Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for 3- 6 months (according tot he treatment group) after last dose of study drug(s) (where applicable).

Exclusion Criteria:

Metastatic or locally advanced unresectable disease
Uncontrolled hypercalcemia
Concomitant unplanned antitumour therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy)
Treatment with any other investigational medicinal product within 28 days prior to study entry
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP.
Treatment with CYP3A4 inhibitors as well as inducers, unless discontinued 7 days prior to randomization
Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis
Other concomitant or previous malignancy, except: i) adequately treated in-situ carcinoma of the uterine cervix, ii) basal or squamous cell carcinoma of the skin, iii) cancer in complete remission for 5 years
Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
Pregnant or breastfeeding women
Patients with known allergy to any excipients to study drugs
History of myocardial infarction and/or stroke or other arterialthrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration
No features suggestive of myelodysplastic syndrome/ acute myeloid leukemia MDS/ AML
Poorly controlled cardiac arrhythmias
Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, bowel obstruction or inability to take oral medication
Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial
Known history of positive tests for human immunodeficiency virus (HIV) infection, hepatitis A or C virus, acute or chronic active hepatitis B infection
History of severe tumour bleeding or bleeding disorders
No blood transfusion within the 28 days prior to study
Poorly controlled anti-coagulation therapy (INR3.0 on coumadin or heparin compounds)
Palliative radiation therapy within 4 weeks prior to registration
Pregnancy or men or women of reproductive age not agreeing to use contraceptive measures