Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase II Trial of Cetuximab and Dasatinib in Patients With Cetuximab-resistant, Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck and Low Serum IL-6
Brief Summary: This is a single-arm, non-masked, open-label, Phase II study of cetuximab + dasatinib in recurrent Squamous Cell Carcinoma of The Head and Neck (SCCHN) that has recurred after cetuximab-containing therapy (please see attached schema).

The primary endpoint 12-week PFS.


Options:
A: Inclusion Criteria:

* Histologically or cytologically confirmed, head and neck or lung cancers
* Any NSCLC histology is eligible. Stages I, II, IIIA (T3N1 only) or recurrent NSCLC that will be managed with surgery are eligible.
* Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) or lung site will be included.
* Surgical resection of head and neck or lung must be planned, either as primary treatment or salvage. Patients must have tissue available prior to receiving drug(s).
* Age greater then 18 years.
* ECOG performance status 0-2.
* Women of childbearing potential (WOCBP) must have:

  1. A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration
  2. Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped.
  3. Ability to take oral medication (dasatinib must be swallowed whole).
  4. Concomitant Medications
* Patients agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib).
* Patient agrees that IV biphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
* Adequate hematologic, renal and hepatic function.
* Have signed written informed consent including a HIPPA form according to institutional guidelines.

Exclusion Criteria:

* Subjects who fail to meet the above criteria.
* Prior therapy for head and neck or lung cancers is allowed, with the exception of EGFR inhibitors. Any systemic therapy should have been completed at least 30 days prior to study enrollment.
* Pregnancy or breastfeeding. Women (patients or partners of male patients) of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy.
* Any unresolved chronic toxicity grade greater or equal to 2 from previous anticancer therapy (except alopecia and anemia).
* Acute hepatitis, known HIV, or active uncontrolled infection.
* Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
* Prior treatment with an EGFR inhibitor (tyrosine kinase inhibitor).
* Cardiac Symptoms; any of the following should be considered for exclusion:

  1. History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (Coumadin). Patients whose therapy is changed to heparin is eligible.
  2. History of any other cancer except basal cell carcinoma of the skin.
  3. Concurrent medical condition which may increase the risk of toxicity, including:

     \* Pleural or pericardial effusion of any grade
  4. 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).
     * Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.
  5. Concomitant Medications, any of the following should be considered for exclusion:

     \* Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib)
  6. Women who:

     * are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug,
     * have a positive pregnancy test at baseline, or
     * are pregnant or breastfeeding.
  7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
B: Inclusion Criteria:

* Histologically-confirmed diagnosis of unresectable Stage III or metastatic melanoma not amenable to local therapy (excluding uveal or ocular melanoma)
* At least one measurable lesion
* No prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (first line) or one prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (second line)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Archived tissue sample or new biopsy sample
* Female participants of childbearing potential must agree to use effective contraception from Visit 1 to 120 days after the last dose of study drug; male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug

Exclusion criteria:

* Prior treatment with ipilimumab or other anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) agent or any anti-programmed cell death (PD-1 or PD-L2) agent
* Chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or not recovered from adverse events caused by cancer therapeutics administered more than four weeks earlier
* Currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug
* Expected to require any other form of systemic or localized antineoplastic therapy while on study
* On any systemic steroid therapy within one week before the planned date for first dose of randomized treatment or on any other form of immunosuppressive medication
* History of a malignancy (other than the disease under treatment in the study) within 5 years prior to first study drug administration, excluding adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases are eligible
* Severe hypersensitivity reaction to treatment with another monoclonal antibody
* Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
* Active infection requiring systemic therapy
* Known history of Human Immunodeficiency Virus (HIV)
* Known history of or positive for Hepatitis B or C
* Known psychiatric or substance abuse disorder
* Regular user (including recreational use) of illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
* Pregnant or breastfeeding, or expecting to conceive, or father children within the projected duration of the study
* Received a live vaccine within 30 days prior to first dose of study drug
C: 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).
D: 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)

Answer: C