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Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation
This study is currently recruiting participants.
Verified by H. Lee Moffitt Cancer Center and Research Institute, August 2009
First Received: March 5, 2009   Last Updated: August 7, 2009   History of Changes
Sponsors and Collaborators: H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Information provided by: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00858403
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: Dasatinib
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase II Study of Dasatinib in Advanced Non-small Cell Lung Cancer With Ex Vivo and In Vivo Assessment of Tumor Target Modulation

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • To assess whether the extent of inhibition of ERK phosphorylation in lung cancer cells exposed ex vivo to dasatinib significantly differs between patients categorized as progressors or non-progressors through standard RECIST criteria. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Estimate the single agent response rate to dasatinib in this patient population. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • Estimate the 6 month progression free survival rate of dasatinib in this patient population. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • Evaluate toxicity of dasatinib in this patient population. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To assess whether the extent of inhibition of ERK phosphorylation in lung cancer cells exposed in vivo to dasatinib significantly differs between patients categorized as progressors or non-progressors through standard RECIST criteria. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To assess whether the extent of inhibition of SRC and Akt phosphorylation in lung cancer cells exposed ex vivo and in vivo to dasatinib significantly differs between patients categorized as progressors or non-progressors through standard RECIST criteria. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To explore whether the extent of inhibition of ERK, SRC and Akt phosphorylation in lung cancer cells exposed ex vivo to dasatinib will correlate with the drug concentration of dasatinib. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To analyze Kras and EGFR mutation and their correlation to the ERK pathway inhibition and to disease control rate and response. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: March 2009
Estimated Study Completion Date: April 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: Dasatinib
Take tablets of Dasatinib by mouth once a day.

Detailed Description:

Cycle 1 - C1D1: Patients will have complete H&P, CBC, CMP and 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 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. 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 - 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 basis. C2D22: Patients will undergo reevaluation for tumor measurements. This assessment can occur on C2D22 ±7 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, PT, 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00858403

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Aaron Becker, RN, B.S.N.     813-745-4679     aaron.becker@moffitt.org    
Principal Investigator: Eric Haura, M.D.            
Sub-Investigator: Soner Altiok, M.D.            
Sub-Investigator: Scott Antonia, M.D.            
Sub-Investigator: Gerold Bepler, M.D., Ph.D.            
Sub-Investigator: Alberto Chiappori, M.D.            
Sub-Investigator: Jhanelle Gray, M.D.            
Sub-Investigator: Tawee Tanvetyanon, M.D.            
Sub-Investigator: Charles Williams, M.D.            
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Eric Haura, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute ( Eric Haura, M.D. )
Study ID Numbers: MCC-15656, USF IRB 107301, CA180214
Study First Received: March 5, 2009
Last Updated: August 7, 2009
ClinicalTrials.gov Identifier: NCT00858403     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Advanced Non-small Cell Lung Cancer

Study placed in the following topic categories:
Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Dasatinib
Lung Diseases
Non-small Cell Lung Cancer
Protein Kinase Inhibitors
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Dasatinib
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009