Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation

• Status: Terminated
• Trial end date: 2010-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The main purpose of this study is to learn how patients with Advanced Non-Small Cell Lung Cancer (NSCLC) respond to the study drug Dasatinib. The study drug, Dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. The use of Dasatinib in this study is considered experimental.

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

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Bristol-Myers Squibb
• Treatments: Dasatinib

Criteria

Inclusion Criteria:

• Histologically or cytologically documented diagnosis of NSCLC that is advanced/metastatic (Stage IIIB/IV).

• Performance Status (ECOG) 0-2

• Previous chemotherapy with the exception of dasatinib. Patients who have had any type of previous chemotherapy regimens for non-small cell lung cancer are eligible.

• Adequate Organ Function:

• Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN)

• Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN

• Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN)

• Serum Creatinine < 1.5 time the institutional ULN

• Hemoglobin, Neutrophil count, Platelets, prothrombin time (PT), partial thromboplastin time (PTT) all Grade 0-1

• Ability to take oral medication

• Concomitant Medications:

• Agree to discontinue St. Johns Wort while receiving dasatinib therapy

• Agree that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.

• Women of childbearing potential (WOCBP):

• A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration

• 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 Prior to study enrollment.

• Signed written informed consent including a HIPAA form according to institutional Guidelines

Exclusion Criteria:

• No malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 5 years.

• Prior dasatinib therapy.

• Concurrent medical condition which may increase the risk of toxicity, including:

• Patients with severe pulmonary disease that increases the risk of toxicity related to dasatinib-induced pleural effusions. This includes chronic obstructive pulmonary disease or pleural effusions (malignant or benign) requiring chronic oxygen therapy or patients that have had prior pneumonectomy. Patients that have a pulmonary embolism and require oxygen therapy will be excluded but not those patients who have a pulmonary embolism but do not require oxygen therapy. Patients with active pleural effusions not controlled with pleurodesis will be excluded.

• Cardiac Symptoms; any of the following should be considered for exclusion:

• Uncontrolled angina, congestive heart failure or 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 QTc interval on pre-entry electrocardiogram (> 450 msec)

• Patients with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration

• History of significant bleeding disorder unrelated to cancer, including:

• Diagnosed congenital bleeding disorders

• Diagnosed acquired bleeding disorder within one year

• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding

• 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)

1. quinidine, procainamide, disopyramide

2. amiodarone, sotalol, ibutilide, dofetilide

3. erythromycin, clarithromycin

4. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

5. cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

• Women:

• 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,or

• have a positive pregnancy test at baseline

• pregnant or breastfeeding

• Prisoners or persons who are compulsorily detained (involuntarily incarcerated)for treatment of either a psychiatric or physical (e.g., infectious) illness

• Patients on systemic anticoagulation at risk of bleeding related to tumor biopsy that cannot be off anticoagulation per the discretion of their physician.