Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase II Study of Cabazitaxel Versus Methotrexate in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With Platinum-based Therapy.
Brief Summary: In this clinical trial, the investigators want to know if cabazitaxel is more effective than methotrexate for patients with recurrent or metastatic squamous cell carcinoma of the head and neck in palliative treatment.


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: Inclusion Criteria:

* Histologically confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix;
* Locally advanced disease, defined by one of the following criteria: any T, N +, M0 (excluding T1, N1), T3-4, N0, M0;
* Not cancer nasopharynx or paranasal sinuses or salivary glands;
* General conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view;
* No other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed \> three years prior to enrollment in the study and for which the patient has remained continuously free of disease;
* Accessibility to follow-up;
* Signing of informed consent;
* Interval between examinations of local staging and randomization, maximum 3 weeks
* Interval between randomization and initiation of treatment, maximum 2 weeks

Exclusion Criteria:

* Age \<18 years
* ECOG performance status \> 0-1
* Hemoglobin \<9 g / dL
* Counts of granulocytes, total \<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
* Mg \> 0.5 mmol/L
* Pregnancy or lactation
* Presence of allergy to study drug or to the excipients used in their formulation
* Peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
* Hearing loss / tinnitus ≥ grade 3 (CTCAE v3.0)
* One of the following conditions:

  * Myocardial infarction within 12 months prior to randomization
  * Severe congestive heart failure
  * Unstable angina
  * Cardiomyopathy in act
  * Ventricular arrhythmia
  * uncontrolled hypertension
  * Severe psychotic disorders in act
  * Severe infection in act
  * Any other serious illness that could interfere with the administration of the therapy provided by the protocol
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: 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