| Exclusion Criteria: | 1) Women who are pregnant, breastfeeding, or have child-bearing potential and are unwilling/unable to use an acceptable method of contraception for the entire study period and for at least 4 weeks after cessation of the study drugs. All women of child-bearing potential must have a negative pregnancy test prior to first receiving protocol therapy. If the pregnancy test is positive, the patient must not receive dastinib or erlotinib, and must not be enrolled on the study
2) Radiotherapy to ribs, sternum, pelvis, vertebrae or skull within 4 weeks prior to entering the study. (If none of these axial skeletal areas are included in the radiotherapy field, patients may have received palliative radiotherapy to long bones provided that it has ended at least 2 weeks prior to initiation of dasatinib-erlotinib therapy.)
3) Patients with any of the following cardiac problems should be excluded: (a) Uncontrolled angina, congestive heart failure, or myocardial infarction within the previous 6 months; (b) Diagnosed congenital long QT syndrome; (c) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); (d) Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec in women or >440 msec in men). If the automated reading is prolonged, the ECG should be manually over read.
4) Continued from Exclusion #4: (e) Any history of second or third degree heart block unless they currently have a pacemaker; (f) Heart rate < 50 / minute on pre-entry electrocardiogram;(g) Uncontrolled hypertension defined as systolic blood pressure > 150 or diastolic >100;(h) Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.
5) Patients with pericardial effusion > grade 1 (by CTCAE v3.0).
6) Patients with pleural effusion > grade 2 (by CTCAE v3.0). A grade 3 pleural effusion that is managed by a thoracentesis or an indwelling catheter is allowable as long as supplemental oxygen is not required.
7) Patients with any condition that impairs their ability to swallow, retain, or absorb dasatinib or erlotinib tablets are excluded. This includes any condition resulting in an inability to take oral medication, a requirement for IV alimentation, prior surgical procedures that have resulted in chronic malabsorption, or active peptic ulcer disease.
8) Patients with > grade 2 neuropathy
9) Patients with a history of pulmonary fibrosis (other than in a radiated field).
10) Patients with inflammatory bowel disease or uncontrolled chronic diarrhea.
11) Patients with a history of significant bleeding disorder unrelated to cancer, including: (a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease); (b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); (c) Ongoing or recent (</= 3 months) significant gastrointestinal bleeding, defined as clinically evident hematemesis or hematochezia requiring therapeutic intervention.
12) Known HIV-positive patients are ineligible because of the potential for pharmacokinetic interactions between dasatinib and antiretroviral therapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
13) Pts currently receiving any of the following medications will be excluded: (a) Any concurrent systemic anticancer therapy; (b) Any concurrent investigational agents (c) Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Pts must discontinue such drugs 7 days or more prior to starting dasatinib):i. quinidine, procainamide, disopyramide;ii. amiodarone, sotalol, ibutilide, dofetilide;iii. erythromycin, clarithromycin;iv. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
14) Continued from Exclusion#14:v.cisapride,bepridil,droperidol,methadone,arsenic, chloroquine,domperidone,halofantrine,levomethadyl,pentamidine,sparfloxacin, lidoflazine;(d)The concomitant use of H2 blockers or proton pump inhibitors w/ dasatinib is not recommended.The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in pts receiving dasatinib therapy.If antacid therapy is needed,the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of dasatinib.
15) Continued from Exclusion #15: (e)Pt may not be receiving any prohibited CYP3A4 inhibitors Potent inhibitors of CYP3A4 are prohibited during study; for such medications, a wash-out period of 7 days is required prior to starting dasatinib. Potent CYP3A4 inhibitors include: · itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib, isoniazid, ketamine nefazodone, nicardipine, propofol, quinidine, telithromycin. (f) St.Johns Wort
16) The patient has received prior investigational therapy, chemotherapy, radiotherapy, or major surgery within 3 weeks of initiating study drug. |