Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Study of Standard Fractionation Radiotherapy With Concurrent High-Dose Cisplatin Versus Accelerated Fractionation Radiotherapy With Panitumumab in Patients With Locally Advanced Stage III and IV Squamous Cell Carcinoma of the Head and Neck
Brief Summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in higher doses over a shorter period of time may kill more tumor cells and have fewer side effects. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving standard radiation therapy together with high-dose cisplatin is more effective than giving higher-dose radiation therapy together with panitumumab in treating patients with locally advanced head and neck cancer.

PURPOSE: This randomized phase III trial is comparing two radiation therapy regimens to see how well they work when given together with cisplatin or panitumumab in treating patients with locally advanced stage III or stage IV head and neck cancer.


Options:
A: Inclusion Criteria:

1. Recurrent and/or metastatic head and neck squamous cell carcinoma not amenable to curative treatment with surgery and/or chemotherapy and/or radiation.
2. At least one measurable lesion by MRI or CT-scan according to RECIST 1.1.
3. Progressive disease within 1 year after first line platinum-based chemotherapy given either as a part of the multimodal curative treatment or in the palliative setting.
4. ECOG performance status 0 -2, in stable medical condition
5. Patients must have an expected survival of at least 3 months
6. Paraffin-embedded tumor tissue available for immunohistochemistry but not mandatory
7. Patients must be over 18 years old and must be able to give written informed consent.
8. Women of child-bearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to enrollment).
9. Patients must have adequate organ function (Hemoglobin ≥ 9 g/100 ml, Neutrophils ≥ 1,500/mm3, Platelets ≥ 100,000/mm3, total bilirubin \<1 time the upper limit of normal (ULN) for age, serum alanine aminotransferase (ALT) \< 1.5 1.5 x ULN for age, aspartate aminotransferase (AST) \< 1.5 ´ ULN for age , serum creatinine \<1.5 x ULN for age.
10. Signed informed consent prior to beginning protocol specific procedure.
11. Sexually active patients must use effective contraception during the period of therapy and up to 150 days after the last treatment dose. Acceptable contraception includes, but is not limited to: oral hormone therapy, partner vasectomy, or double barrier contraception (which is defined as a male condom plus spermicide in combination with either a female condom, or diaphragm, or cervical cap or intrauterine device)

Exclusion Criteria:

1. Non-squamous head and neck cancer
2. Nasopharynx cancer
3. More than two lines of chemotherapy for palliative treatment
4. Surgery or investigational drugs or chemotherapy within 4 weeks before study inclusion. Curative radiation therapy (60-70 Gy) within 8 weeks. For palliative radiation therapy (i.e 8 Gy on a painful lesion) no delay is needed.
5. Previous treatment with cabazitaxel
6. Significant active cardiac disease including: uncontrolled high blood pressure according to the CTCAE 4 grading, unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias
7. Other uncontrolled illnesses (active infections requiring antibiotics, bleeding disorders, uncontrolled diabetes ...)
8. Previous malignancy from which the patient has been disease-free for \< 5years, as other than SCCHN.
9. Previous treatments with taxanes and/or anti-EGFR therapy are not an exclusion criteria.
10. Active grade \> 2 peripheral neuropathy
11. Active grade \> 2 stomatitis
12. Known brain or leptomeningeal involvement
13. History of severe hypersensitivity reaction (\> grade 3) to polysorbate 80 containing drugs
14. Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A/5. A one-week washout period is necessary for patients who are already on these treatments.
15. Organic brain syndrome or significant psychiatric abnormality that would preclude participation in the full protocol and follow up.
B: DISEASE CHARACTERISTICS:

* Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

  * Locally advanced disease, defined by any of the following criteria:

    * Any T, N+, M0
    * T3-4, N0, M0
* No current history of unknown primary squamous cell carcinoma of the head and neck, primary nasopharyngeal, paranasal, or salivary gland tumors of the head and neck

PATIENT CHARACTERISTICS:

* ECOG performance status 0-1
* Absolute granulocyte count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT ≤ 3 times ULN
* Creatinine clearance \> 50 mL/min
* Magnesium \> 0.5 mmol/L
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
* Must be accessible for treatment and follow-up
* Able (sufficiently fluent) and willing to complete the quality of life (QOL) and swallowing QOL questionnaires in either English or French
* Must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation
* No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors
* No history of allergic or hypersensitivity reactions to any of the study drugs or their excipients
* No prior or concurrent interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) on baseline CT scan
* No peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
* No hearing loss/tinnitus ≥ grade 3 (CTCAE v3.0)
* No thromboembolic event within the past 12 months despite being treated with anticoagulation drugs

  * Prior thromboembolic event \> 12 months allowed provided patient is stable on anticoagulation or on preventative anticoagulation
* None of the following allowed:

  * Myocardial infarction within the past 12 months
  * Uncontrolled severe congestive heart failure
  * Unstable angina
  * Active cardiomyopathy
  * Unstable ventricular arrhythmia
  * Uncontrolled hypertension
  * Uncontrolled psychiatric disorder
  * Active serious infection
  * Active peptic ulcer disease
  * Any other medical condition that might interfere with protocol therapy delivery

PRIOR CONCURRENT THERAPY:

* No prior surgical treatment except diagnostic biopsy for this disease
* No prior induction chemotherapy for this disease
* No prior radiation to the head and neck region that would result in overlap of fields for this study
* No prior cisplatin or carboplatin chemotherapy
* No prior targeted anti-EGFR therapy of any kind
* At least 30 days since any prior investigational agent
* No concurrent granulocytic growth factors (e.g., filgrastim \[G-CSF\]) during radiotherapy
* No concurrent erythropoietic growth factors, pilocarpine, amifostine, other anticancer therapy (e.g., cytotoxic agents, biological response modifiers, immunotherapy, or hormonal therapy), or other investigational drug therapy
* The following radiological investigations must be done within 8 weeks of randomization:

  * MRI or CT of the head and neck
  * CT chest
C: 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
D: 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.

Answer: B