Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparison of Biomarker Modulation by Inhibition of EGFR and/or Src Family Kinases Using Erlotinib and Dasatinib in Head and Neck Lung Cancers
Brief Summary: The central hypothesis to be tested in this study is that dual blockade of EGFR and Src pathways or proteins are distinct compared to inhibition of either kinase alone in head and neck and lung cancers.


Options:
A: 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)
B: 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
C: Inclusion Criteria:

* Men and women ≥18 years of age
* Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease)
* Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
* Measurable disease by computed tomography (CT)/Magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient

Exclusion Criteria:

* Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent)
* Subjects with carcinomatous meningitis
* Subjects with active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
* Prior therapy with anti-Programmed death-1 (PD-1), anti-Programmed cell death ligand 1 (PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
* Prior treatment on the first line study CA184104 first line NSCLC study
* Prior treatment with Docetaxel
* Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
* Treatment with any investigational agent within 14 days of first administration of study treatment
D: 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.

Answer: D