Clinical trial NCT00858403: Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Advanced Non-small Cell Lung Cancer
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2009-03-09
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 basis.

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

Eligibility 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.

Primary outcomes:
measure: Number of Participant Progressors vs. Non-progressors With Tumor Response
timeFrame: 1 year, 4 months
Secondary outcomes:
measure: Number of Participants With Response to Dasatinib
timeFrame: 1 year, 4 months
measure: Number of Participants With Progression Free Survival (PFS) at 6 Months
timeFrame: 1 year, 4 months
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: 1 year, 4 months
measure: Number of Participant Progressors vs. Non-Progressors With Inhibition Response
timeFrame: 1 year, 4 months
measure: Correlation Between Extent of Inhibition and Concentration of Dasatinib
timeFrame: 1 year, 4 months
measure: Correlation Between Mutation and Inhibition and to Disease Control Rate and Response
timeFrame: 1 year, 4 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Eric Haura, M.D.
role: PRINCIPAL_INVESTIGATOR
References: