Please select the eligibility criteria that correspond to the clinical trial below.
Title: CARISSA Trial - Multicenter Randomized Phase II Trial Comparing Post-operative Radiotherapy and Cisplatin Alone or in Combination With the EGFR Inhibitor ZD 1839 (Iressa) in Upper Aerodigestive Tract Carcinomas
Brief Summary: This trial will be an open multicentric randomized phase II study comparing post-operative radiotherapy + cisplatin associated or not with Iressa in upper aerodigestive tract carcinomas.


Options:
A: Inclusion:

* Patients must have metastatic and/or recurrent SCCHN that has been previously treated with cetuximab.
* Undetectable baseline serum IL-6 NOTE : This eligibility criterion applies only to patients enrolling to the second, biomarker-enrichment stage of the trial.
* Measurable disease per RECIST 1.1.
* Unlimited prior treatment with radiation or chemoradiotherapy
* Any number of prior regimens for recurrent or metastatic SCCHN (i.e. palliative treatment) including cetuximab or other EGFR inhibitor
* Age \>18 years
* ECOG performance status \<2 (Karnofsky \>60%, see Appendix A).
* Life expectancy of greater than 12 weeks.
* Patients must have normal organ and marrow function as defined below:

  1. absolute neutrophil count \>1,200/µL
  2. platelets \>100,000/µL
  3. total bilirubin within normal institutional limits
  4. AST(SGOT)/ALT(SGPT) \< 2.5 X institutional upper limit of normal
  5. Creatinine up to 1.5 X normal institutional limits
* Ability to understand and the willingness to sign a written informed Consent document.
* Patients should not be taking concomitant medication that are CYP3A4 inducers or potent inhibitors and should try to avoid taking proton pump inhibitors and H2 antagonists during rest of treatment period. The above medications will be continued only if medically necessary and their use will be noted.
* Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. All WOCBP MUST have a negative pregnancy test prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.

Exclusion:

* Patients who have not recovered from adverse events due to prior agents. A minimum interval of 3 weeks should have elapsed from prior chemotherapy other than cetuximab. A minimum of 12 weeks should have elapsed from prior definitive radiotherapy, and a minimum of 1 week should have elapsed from prior palliative radiotherapy.
* Patients may not have received an investigational agent within 4 weeks of starting this trial.
* Patients with untreated brain metastases should be excluded from this clinical trial.
* History of allergic reactions to monoclonal antibodies.
* Inability to swallow oral medications (unless patients use a feeding tube in which case they are eligible).
* Uncontrolled angina or uncontrolled hypertension or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
* Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec) on the Bazett's correction.
* Diagnosed or suspected congenital long QT syndrome.
* Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
* Any other uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements.
* History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
B: Inclusion Criteria:

* Cytological or pathological documented squamous cell carcinoma of oral cavity, oropharynx, larynx, and hypopharynx; patients with nasopharyngeal carcinoma can be included if the patients have grades I or II tumors according to the World Health Organization (WHO) classification
* Stage III or IV according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Sixth Edition (2002)
* Unresectable or resection with significant morbidity
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Measurable Disease, defined according to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
* Bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN
* Calculated creatinine clearance \>= 55ml/min (using the Cockcroft-Gault formula)
* Platelet count \>= 100 x 10\^9 /L
* Absolute neutrophil count (ANC) \>= 1.25 x 10\^9 /L
* Signed informed consent
* Male and female patients with reproductive potential must use an acceptable contraceptive method
* Authorization from a dentist to begin radiation therapy

Exclusion Criteria:

* Second primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollment
* Inability or unwillingness to comply with radiotherapy
* Evidence of clinically significant congestive heart failure; patients must be able to tolerate hydration required during cisplatin chemotherapy
* Diarrhea \> grade 1 at the time of enrollment
* Prior radiotherapy, chemotherapy, or investigational treatment for squamous cell carcinoma of head and neck
* Prior treatment with an investigational or marketed inhibitor of the EGFR pathway
* Use of cytochrome P450 3A4 (CYP3A4) inducers
* Presence of systemic metastases (M1)
* Pregnant or breast-feeding women
* Known human immunodeficiency virus (HIV) infection
C: Inclusion Criteria:

* Patients with upper aerodigestive tract carcinomas (all sites included) having surgical resection and eligible for post-operative radiation + cisplatin.
* Patient having a tumoral biopsy (0.5 - 1 cm3) stored in liquid nitrogen at time of surgical resection (patients with small tumors located in larynx for instance will not be included)
* Patients receiving post-operative radiation (\>=60 Gy on tumor bed and/or cervical area), associated with cisplatin, 6 weeks after surgery at the latest.

Exclusion Criteria:

* previous history of cancer (except skin basal cell carcinoma)
D: Inclusion criteria:

1. Histologically or cytologically confirmed loco-regionally advanced head and neck squamous cell carcinoma (HNSCC), stage III to IVb
2. Unresected tumour prior to chemo-radiotherapy (CRT)
3. Concomitant CRT completed prior to randomisation
4. After concomitant platinum-based CRT, no evidence of disease (NED) on clinical and radiographic examinations
5. Eastern cooperative oncology group (ECOG) performance status 0 or 1

Exclusion criteria:

1. Prior treatment with epidermal growth factor receptor (EGFR)-targeted small molecules, EGFR-targeted antibodies, and/or any investigational agents for HNSCC
2. Patients with smoking history of less than or equal to 10 pack years and with primary tumour site of base of tongue and/or tonsil
3. Any other malignancy (except for simultaneous HNSCC primaries, appropriately treated superficial basal cell skin cancer and surgically cured cervical cancer in situ) unless free of disease for at least five years
4. Known pre-existing Interstitial Lung Disease (ILD)
5. Pregnancy or breast feeding

Answer: C