Please select the eligibility criteria that correspond to the clinical trial below.
Title: Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin
Brief Summary: A phase III trial of induction chemotherapy followed by definitive radiotherapy plus Cetuximab versus chemoradiation in unresectable, locally advanced, squamous cell carcinoma of the head and neck (HNC).


Options:
A: Inclusion Criteria:

1. WHO II-III carcinoma of the nasopharynx, histologically proven by a nasal cavity biopsy, locally advanced T2b, T3, T4 and/or N1, N2 or N3 (UICC/AJCC2002).
2. Absence of distant metastases, confirmed by a chest CT scan, abdominal ultrasound (or CT scan) in case of abnormal hepatic function, and bone scintigraphy required.
3. Total absence of previous chemotherapy or radiotherapy, for whatever reason.
4. Total absence of surgical procedures for nasopharyngeal carcinoma.
5. Total absence of concurrent cancer treatment.
6. Total absence of chronic treatment (\>= 3 months) with corticosteroids with a daily dosage \>= 20 mg/day of methylprednisolone or equivalent.
7. Age between 18 and 70 years.
8. Performance status 0 or 1 according to the WHO criteria.
9. Hematological function parameters performed within 10 days before inclusion:

   * Neutrophils \>= 1.5 \* 109/l
   * Platelets: \>= 100 \* 109/l
   * Hemoglobin: \>= 10 g/dl
10. Hepatic function parameters performed within 10 days before inclusion:

    * Total bilirubin is normal
    * AST (SGOT) and ALT (SGPT) \<= 2.5 \* upper limit of normal (ULN) of each center.
    * Alkaline phosphatase \<= 2.5 \* ULN.
11. Renal function parameters performed within 10 days before inclusion: Creatinine clearance must be \<= 55 ml/min.
12. Patient who has given his/her written consent before any specific procedure of the protocol.
13. Patient having a Social Security (social policy-holders)

Exclusion Criteria:

1. WHO I carcinoma of the nasopharynx, histologically proven by a nasal cavity biopsy.
2. Other previous or concomitant cancer, except for in situ cervical cancer and cutaneous basal cell carcinoma.
3. Histological diagnosis on a lymph node biopsy.
4. Pregnant or breast-feeding females, or females and males of childbearing potential not taking adequate contraceptive measures.
5. Symptomatic peripheral neuropathy with grade \>= 2 according to the NCI-CTC criteria.
6. Other serious concurrent medical disease (non-exhaustive list):

   * Unstable heart disease despite treatment.
   * Myocardial infarction within 6 months before inclusion in the trial.
   * A history of neurological or psychiatric events such as dementia, convulsions.
   * Severe uncontrolled infection.
   * Active gastroduodenal ulcer.
   * Obstructive Pulmonary Disease requiring hospitalization within the year prior to inclusion.
7. Clinical impairment of auditory function.
8. The presence, at time of screening, of psychological, familial, social or geographical factors that may have an effect on the compliance of the patient with the study protocol and monitoring comprises an exclusion criterion. These factors must be discussed with the patient before his or her inclusion in the trial.
9. Hypersensitivity to the excipients.
10. A patient already enrolled in another therapeutic trial on an investigational compound.
11. A person deprived of liberty or in the care of a guardian.

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B: DISEASE CHARACTERISTICS:

* Histologically proven advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx

  * Stage III OR
  * Stage IV without distant metastases
* Measurable disease
* Tumor tissue available for immunohistochemical assay of epidermal growth factor receptor expression

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* At least 1 year

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* SGOT and SGPT no greater than 2 times upper limit of normal

Renal:

* Creatinine no greater than 1.5 mg/dL OR
* Creatinine clearance at least 50 mL/min
* Calcium normal

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Medically able to withstand a course of definitive radiotherapy
* No medical or psychologic condition that would preclude informed consent or compliance
* No other malignancy within the past 3 years except basal cell skin cancer or preinvasive carcinoma of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior cetuximab or other murine monoclonal antibody

Chemotherapy:

* At least 3 years since prior systemic chemotherapy
* No concurrent chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy to head and neck
* No other concurrent radiotherapy

Surgery:

* No prior surgery for indicator lesion except biopsy
* Study radiotherapy must not be a part of a postoperative regimen after primary surgical resection
C: 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.
D: 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

Answer: D