Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Randomized Trial of Avelumab-cetuximab-Radiotherapy Versus Standards of Care in Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Brief Summary: The purpose of this study is to demonstrate that treatment with avelumab in combination with RT-cetuximab is superior to standard of care (SOC) cisplatin-RT and/or to SOC RT-cetuximab alone in terms of progression-free survival (PFS) in front-line patients with locally advanced SCCHN.


Options:
A: Inclusion Criteria:

* \> 18 years of age
* Histologically or cytologically confirmed diagnosis of HNSCC
* Stage III/IV, not suitable for surgery (definitive cure rate improbable, technically unresectable or medical contraindication for surgery)
* At least one uni-dimensional measurable lesion either by CT scan or MRI
* Signed written informed consents prior to beginning protocol

Specific procedures:

* Tumor tissue available for immunohistochemical staining of EGFR expression and HPV
* Life expectancy of \> 3 months at study entry
* ECOG Performance Status of \<2 at study entry.
* Effective contraception if risk of conception exists.
* Neutrophils \> 2.0/mm³, platelet count \> 100,000/mm³, and hemoglobin \> 10 g/dl
* Normal liver function
* Serum creatinine \> 1.25 x ULN and/or creatinine clearance \> 60 ml/min

Exclusion Criteria:

* Prior systemic chemotherapy and/or radiotherapy
* Known peripheral neuropathy \> grade 2 NCI-CTC version 3.0
* Known chronic heart failure
* Prior surgery, excluding prior diagnostic biopsy
* Known drug abuse
* Active uncontrolled infection
* Other concomitant anticancer therapy
* Distant metastasis
* Concurrent chronic systemic immune therapy, chemotherapy for disease other than cancer, or hormone therapy not indicated in the study protocol
* Clinically relevant coronary artery disease or history of a myocardial infarction within the last 12 months before study entry
* Medical or psychological condition that would not permit the patient to complete the trial or sign informed consent
* Nasopharyngeal carcinoma WHO type II or III
* Known allergic reaction against any of the components of the treatment
* Pregnancy (absence confirmed by beta-HCG test) or lactation period
* Any prior or on-going investigational medication
* Previous or current malignancy except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
B: Inclusion Criteria:

1. Age ≤ 80 years
2. Performance Status ECOG 0-1
3. Squamous cell carcinoma, previously untreated
4. Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)
5. Oral cavity, oropharynx, hypopharynx or larynx
6. Availability of pre-treatment tumour tissue sample (for p16 \& PD -L1 expression, TILs and immune landscape)
7. Recording of alcohol consumption and smoking history
8. Determination of the patient's ability to receive cisplatin 100 mg /m2 for 3 cycles (fit / unfit)\*
9. Written informed consent

   * Criteria for determining if a patient is fit for receiving high dose cisplatin:

     * Calculated creatinin clearance ≥ 60 mL/min as determined by the modified. method of Cockcroft and Gault or by the EDTA method
     * Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, hemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin \> 35 g/L
     * Peripheral neuropathy \< grade 2
     * No clinical hearing loss (confirmed by audiogram)
     * Cardiac function compatible with hyperhydration; Left ventricular ejection fraction within the institutional normal ranges as measured by echocardiogram

Exclusion Criteria:

1. Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
2. Squamous cell carcinoma involving cervical neck nodes with unknown primary site
3. Metastatic disease (stage IVc)
4. Viral infection (HIV, Hepatitis B/C)
5. Autoimmune disease
6. Immunodeficiency or immunosuppressive therapy
7. Active CNS disease
8. Interstitial lung disease
9. Active infection
10. Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior surgical resection or RT, or use of any investigational agent
11. Weight loss of \> 10% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
12. Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
13. Concomitant treatment with any drug on the prohibited medication list such as live vaccines
14. History of other malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas)
15. Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
16. Known hypersensitivity reaction to study drugs
17. Any social, personal, medical and/or psychological factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.
C: Inclusion Criteria:

* 1.Histologically or cytologically proven squamous cell carcinoma of the head/neck.
* 2.Primary tumor sites eligible: oral cavity, oropharynx, hypopharynx, larynx. Although they are admittedly of squamous cell types, the following tumors will be excluded because their responsiveness to chemotherapy may differ: nasal, paranasal cavities; nasopharynx.
* 3.Stage 3 or 4 disease without evidence of distant metastases verified with Chest X-Ray, abdominal ultrasound or CT (liver function test abnormalities); bone scan in case of local symptoms.
* 4.At least one uni or bidimensionally measurable lesion.
* 5.Tumor considered as inoperable after evaluation by a multidisciplinary team (surgeon, medical oncologist and radiation oncologist). Criteria include : Technical unresectablility-ie tumor fixation/invasion to base of the skull or cervical vertebrae involvement of the nasopharynx and fixed lymph nodes; Physician's decision based on low surgical curability which includes all T3-4 stages, all N2-3 stages excluding T1N2; organ preservation.
* 6.No previous chemotherapy or radiotherapy for any reason and no previous surgery for SCCHN (other than biopsy) are allowed at time of study entry.
* 7.Age ³ 18 years.
* 8.WHO performance status of 0-1
* 9.No active alcohol addiction
* 10.Life expectancy ³ 12 weeks
* 11.Signed informed consent prior to beginning protocol specific procedures
* 12.Adequate bone marrow, hepatic and renal functions as evidenced by the following: Hematology (Bone Marrow): Neutrophil count ³ 2.0 x 10 9/L; Platelet count ³ 100 X 10 9/L; Hemoglobin ³ 10g/dL; Hepatic function : Total bilirubin WNL; ASAT (SGOT) and ALAT (SGPT) £ 2.5 X ULN; Alkaline phosphatase £ 5 X ULN; patients with ASAT or ALAT \> 1.5 x ULN associated with alkaline phosphatase \> 2.5 x ULN are not eligible for the study; Renal function: the creatinine clearance ³ 60 ml/min (actual or calculated by the Cockcroft-Gault method as follows: Weight (kg) X (140-age)/K x serum creatinine.
* 13.Patients must be available for treatment and follow up. Patients registered on this trial must be treated and followed at the participating center.

Exclusion Criteria:

* 1.Pregnant or lactating women or women of childbearing potential not using adequate contraception.
* 2.Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma of the skin or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years. Any prior treatment with radiotherapy or chemotherapy is an exclusion criterion.
* 3.Symptomatic peripheral neuropathy ³ grade 2 by NCIC-CTG criteria.
* 4.Symptomatic altered hearing \> grade 2 by NCIC-CTG criteria.
* 5.Other serious illnesses or medical conditions including but no limited to: Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry; History of significant neurologic or psychiatric disorders including dementia or seizures; Active uncontrolled infection; Active peptic ulcer; Hypercalcemia; Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry.
* 6.Patients requiring intravenous alimentation.
* 7.Patients who experienced a weight loss of more than 20% of their body weight in the 3 months preceding study entry.
* 8.Concurrent treatment with any other anticancer therapy
* 9.Participation in an investigational trial within 30 days of study entry.
D: Inclusion Criteria:

* Meets protocol-specified criteria for qualification and contraception
* Is willing and able to comply with study procedures and restrictions related to food, drink and medications
* Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

* Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
* Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff;
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
  3. the analysis of results

Answer: B