Intervention: Dasatinib
Trial phase: Phase 2
ATC code: L01EA02 | L01XE06
SMILES: Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCO)CC2)n1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2
Group description: Neoadjuvant dasatinib is to be administered as an oral dose of 70 mg PO twice daily on a continuous basis for 3 weeks prior to surgery. Patients will begin adjuvant dasatinib (70 mg PO twice daily) between 4-6 weeks after standard adjuvant therapy is complete or 4-8 weeks after surgery for those patients that do not receive adjuvant chemotherapy. Adjuvant dasatinib will be given on a continuous basis for up to 3 months after adjuvant chemotherapy or after surgery if no adjuvant chemotherapy is given.
Eligibility criteria:
Inclusion Criteria:

Suspected or histological/cytological diagnosis of Non-Small Cell Lung Cancer (NSCLC), Stage IB (≥4 cm per CT) or Stage IIA or IIB, amenable to surgical resection
Must be deemed a surgical candidate
Tumors ≥2 cm in maximum diameter without radiographic, bronchoscopic or pathologic evidence of nodal metastases are eligible for biopsy
Fresh tissue biopsy material must be available for genomics analysis prior to initiating dasatinib therapy
Age ≥18 years
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
No prior chemotherapy, immunotherapy, radiation therapy or biologic/targeted therapy for any malignancy

Adequate Organ Function:

Total bilirubin <institutional upper limit normal (ULN)
Hepatic enzymes (AST, ALT) ≤2.5x institutional ULN
Serum creatinine <1.5x institutional ULN
Hemoglobin ≥9 gm/dL
Neutrophil count (ANC or AGC) ≥1500 per μL
Platelets ≥100,000 per μL
Prothrombin time (PT)/a partial thromboplastin time (PTT) ≤1.5x control
No other serious medical or psychiatric illness
Ability to take oral medication (dasatinib must be swallowed whole)
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test preferably within 72 hours and no later than 7 days, prior to the start of study drug administration
Both sexually active males and females of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped
Signed written informed consent including Health Insurance Portability and Accountability Act (HIPAA) according to institutional guidelines

Exclusion Criteria:

Previous or concomitant malignancy in the past 2 years other than curatively treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin
Prior dasatinib therapy
Evidence of pleural or pericardial effusion of any grade

Cardiac Symptoms:

Uncontrolled angina, congestive heart failure (CHF), or myocardial infarction (MI) within 6 months
Diagnosed congenital long QT syndrome
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes)
Prolonged QT corrected (QTc) interval on pre-entry EKG (>450 msec)
Uncontrolled hypertension defined as >160/90 on a regimen of antihypertensive therapy
Subjects with hypokalemia or hypomagnesaemia if it cannot be corrected
History of diagnosed congenital acquired bleeding disorders (e.g., von Willebrand's disease)
Ongoing or recent (≤3 months) significant (≥grade 3) gastrointestinal bleeding

Concomitant Medications:

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)

**quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine

Current therapeutic dose heparin or coumadin therapy
St. John's Wort and all herbal supplements must be stopped while on dasatinib
IV bisphosphonates will be withheld for 2 weeks prior and 6 weeks after dasatinib administration due to risk of hypocalcaemia
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
Pregnant or breastfeeding
Active or uncontrolled infection requiring intravenous antibiotics
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dasatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
Patients who have received investigational drugs ≤4 weeks prior to starting study drug and/or who have not recovered from side effects of such therapy