Phase II Study Evaluating The Safety And Response To Neoadjuvant Dasatinib In Early Stage Non-Small Cell Lung Cancer

• Status: Terminated
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Src expression has been identified in a majority of Non-Small Cell Lung Cancer (NSCLC) cell lines and there is preclinical evidence that Src family kinases may be important in hypoxic growth and angiogenesis in NSCLC. We hypothesize that the inhibition of Src pathway with dasatinib will demonstrate anti-tumor activity in early stage NSCLC, with a tolerable safety profile.

Patients will receive dasatinib, a Src inhibitor, for 3 weeks prior to surgical resection for early stage NSCLC. Fresh frozen tumor tissue is needed for genomic analysis. If fresh frozen tumor tissue is not available from the initial diagnosis, a biopsy will be required to participate in this trial. A second tumor sample will be obtained at time of surgical resection to evaluate for changes in genomic expression profiles.

Patients will be eligible to receive 3 months of adjuvant dasatinib therapy after completion of standard adjuvant therapy or after recovery from surgery if no standard adjuvant therapy is given, if there is evidence of neoadjuvant tumor response (radiologic and/or pathologic) to dasatinib.

Many patients who present with NSCLC are active smokers. Patients who are smoking up until the time of their surgery experience increased peri-operative complications compared to patients who have not smoked cigarettes immediately prior to surgery. While this trial will not be limited to active smokers, the period of smoking cessation prior to surgery is an attractive window of opportunity during which the potentially active novel anticancer therapy dasatinib can be offered to the patient.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: Bristol-Myers Squibb
• Treatments: Dasatinib

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- 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