Please select the eligibility criteria that correspond to the clinical trial below.
Title: Neoadjuvant Docetaxel+Cisplatin and 5-fluorouracil (TPF) Followed by Radiotherapy+Concomitant Chemo or Cetuximab Versus Radiotherapy+Concomitant Chemo or Cetuximab in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. A Randomized Phase III Factorial Study.
Brief Summary: This is a randomized multicenter open label phase III factorial trial evaluating the 3 years OS in patients with locally advanced squamous cell carcinoma of head and neck treated with locoregional treatment (radiotherapy plus concomitant chemotherapy or cetuximab) with or without neoadjuvant chemotherapy.


Options:
A: Inclusion Criteria:

1. Histologically or cytologically proven squamous cell carcinoma of the head and neck.
2. Primary tumor sites eligible : oral cavity, oropharynx, hypopharynx Although they are admittedly of squamous cell types, the following tumors will be excluded because of them responsiveness to chemotherapy: tumors of the nasal and paranasal cavities and of the nasopharynx.
3. Stage 3 or 4 disease without evidence of distant metastases verified by 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 inoperable after evaluation by a multidisciplinary team (i.e. a surgeon, a medical oncologist and a radiation oncologist). Criteria for inoperability are:

   1. technical unresectability: tumor fixation/invasion to base of the skull or cervical vertebrae, involvement of the nasopharynx, and fixed lymph nodes.
   2. Physician decision based on low surgical curability. This category will include the following:

   i) All T3-4 stages. ii) All N2-3 stages excluding T1 N2. iii) Patients for organ preservation. Reason for inoperability will be recorded in the CRF.
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 \> 18 years.
8. Karnofsky performance status \> 70. (ECOG 0-1) (Appendix II)
9. No active alcohol addiction.
10. Life expectancy \> 6 months.
11. Signed informed consent prior to beginning protocol specific procedures.
12. Adequate bone marrow, hepatic and renal functions as evidenced by the following:

    a) Hematology (Bone marrow): i) Neutrophils \> 2.0 109/L ii) Platelets \> 100 x 109/L iii) Hemoglobin \> 10 g/dL b) Hepatic function i) Total bilirubin \< 1 x UNL ii) ASAT (SGOT) and ALAT (SGPT) \< 2.5 x ULN iii) 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.

    c) Renal function : serum creatinine \< 1 x UNL. In case of borderline value the creatinine clearance \> 60 ml/min (calculated by the Cockcroft-Gault method as follows :
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 \> grade 2 by NCIC-CTG criteria
4. Symptomatic altered hearing \> grade 2 by NCIC-CTG criteria.
5. Other serious illnesses or medical conditions including:

   1. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry.
   2. History of significant neurologic or psychiatric disorders including dementia or seizures.
   3. Active uncontrolled infection.
   4. Active peptic ulcer.
   5. Hypercalcemia.
   6. Chronic obstructive pulmonary disease requiring hospitalization during the year preceding study entry
6. History of hypersensitivity reaction to polysorbate 80 (Appendix IV)
7. Patients requiring intravenous alimentation.
8. Patients who experienced a weight loss of more than 20% of their body weight in the 3 months preceding study entry.
9. Concomitant treatment with any other anticancer therapy.
10. Participation in a therapeutic clinical trial within 30 days of study entry
B: 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
C: Inclusion Criteria:

* Histologically proven, locally advanced stage III-IV A-B (UICC 2002) primary squamous cell carcinoma of the oral cavity, the oropharynx, the hypopharynx, the supraglottic larynx
* Age ≥ 18
* Written informed consent for the participation in the clinical trial

Exclusion Criteria:

* Inadequate hepatic function: Bilirubin \> 2,0 mg/dl, SGOT, SGPT, AP, Gamma-GT \> 3 x ULN
* Inadequate bone marrow function: leukocytes \< 3,5 x 10\^9/l, platelets \< 100 x 10\^9/l or neutrophils \< 1,5 x 10\^9/l
* Serum creatinine \> 1,5 mg/dl, creatinine clearance \< 60ml/min
* Uncontrolled severe somatic or psychological disease: e.g. unstable angina pectoris; myocardial infarction during the last 6 months; significant cardial rhythm disorders; apoplexy; high grade stenosis of the carotis; neurological or psychiatric disorders including convulsive disorders; dementia; psychosis; active uncontrolled infection or sepsis; liver cirrhosis; Child stage B,C; severe liver function disorders; marginal changes in the blood count; severe kidney damage; HIV-infection
* Acute infections
* Fertile women without adequate contraception during and up to 6 months after therapy (the method of contraception has to be high effective as described in the Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95 mod) and it has to be discussed with the investigator)
* Pregnant or breast feeding women
* Men, who are not willing to use adequate contraception during and up to 6 months after therapy, that is discussed with the investigator
* ECOG-Status \> 1
* Reduced hearing function (especially higher frequencies)
* Exsiccosis
* Neuropathy, caused by cisplatin
* Concurrent malignancies, with exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma or the cervix
* Prior radiotherapy of the neck or chemotherapy
* Distant metastasis
* Recurrent carcinoma in the head and neck region
* Prior neck-dissection or surgical intervention exceeding an exploratory excision
* Known intolerance to 5-Fluorouracil
* Known deficit of Dihydropyrimidine dehydrogenase (DPD)
* Simultaneous therapy with Brivudin or other inhibitors of DPD
* Known intolerance to Cisplatin or other substances that contain platin
* Known intolerance to Paclitaxel or one of the included substances, especially to Poly(oxyethylene)Rhizinusöl/Macrogolglycerol ricinoleate
D: 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

Answer: A