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Phase II Study of Dasatinib in Advanced Non-small Cell Lung Cancer With Ex Vivo and In Vivo Assessment of Tumor Target Modulation

Phase 2
18 Years
Not Enrolling
Lung Cancer

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Trial Information

Phase II Study of Dasatinib in Advanced Non-small Cell Lung Cancer With Ex Vivo and In Vivo Assessment of Tumor Target Modulation

Cycle 1 Day 1 (C1D1): Patients will have complete history and physical (H&P), complete blood
count (CBC), complete metabolic panel (CMP) and electrocardiogram (EKG) on day 1. Each cycle
is 28 days. The C1D1 EKG can be omitted if the patient has no new cardiac symptoms and has
not starting taking any medication known to affect QT corrected for heart rate (QTc)
prolongation. Any residual toxicity from prior therapy for cancer will be recorded. Blood
will be drawn for assessment of serum markers. The patient will begin dasatinib at the
starting C1D1 on a daily basis.

Cycle 1 Day 10-20 (C1D10-20): Patients will have a second biopsy to obtain additional tumor
material to examine biological effects of dasatinib on signaling pathways. Dasatinib will be
taken first thing in the morning and the patient will log the time. Blood will also be drawn
for pharmacokinetic assessments of dasatinib levels in plasma and the time recorded. Four
FNA aspirates and 2 core biopsies can be obtained either at the bedside for palpable lesions
or through appropriate image-guided techniques (CT or US) at the discretion of the treating
physician in consultation with radiology. The time of the biopsy will be recorded. One core
biopsy should be immediately fixed in formalin and the other core biopsy should be snap
frozen in liquid nitrogen.

Cycle 2 Day 1 (C2D1): Patients will be seen by the treating physician and have complete H&P,
CBC, and CMP. Blood will be drawn for assessment of serum markers. Toxicity of dasatinib
will be assessed. The patient will continue to take daily doses of dasatinib on a daily

Cycle 2 Day 22 (C2D22): Patients will undergo reevaluation for tumor measurements. This
assessment can occur on C2D22 ±7 days.

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

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

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,

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participant Progressors vs. Non-progressors With Tumor Response

Outcome Description:

We planned to assess whether the extent of inhibition of extracellular signal-regulated protein kinase (ERK) phosphorylation in lung cancer cells exposed ex vivo to dasatinib significantly differed between patients categorized as progressors or non-progressors through standard Response Evaluation Criteria In Solid Tumors (RECIST)

Outcome Time Frame:

1 year, 4 months

Safety Issue:


Principal Investigator

Eric Haura, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

March 2009

Completion Date:

July 2010

Related Keywords:

  • Lung Cancer
  • Advanced Non-small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida  33612