Clinical trial NCT00459342: Dasatinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official title: Phase II Study of Dasatinib in Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-04-11
Enrollment: 35
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: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well dasatinib works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Detailed description: PRIMARY OBJECTIVES:

I. Determine the progression-free survival at 12 weeks in patients with stage IIIB or IV or recurrent non-small cell lung cancer treated with dasatinib.

SECONDARY OBJECTIVES:

I. Determine the rate of response in patients treated with this drug. II. Examine the relationship between clinical response to this drug and epidermal growth factor receptor (EGFR) mutational status, EGFR copy number, and (phosphorylated Src) pSrc expression levels in pre-treatment tumor biopsies.

III. Determine the toxicity of this drug.

OUTLINE:

Patients received oral dasatinib twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Previously obtained paraffin-embedded tumor tissue samples are analyzed by polymerase chain reaction and fluorescent in situ hybridization (FISH) for epidermal growth factor receptor and by immunohistochemistry for pSrc expression.

Eligibility criteria: Inclusion Criteria:

* Platelet count \>= 100,000/mm\^3
* Histologically or cytologically confirmed non-small cell lung cancer meeting 1 of the following criteria:

  * Stage IV disease
  * Stage IIIB disease with pleural effusion
  * Recurrent disease after surgery or radiotherapy
* Measurable disease, defined as \>= 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan
* Previously treated brain metastasis allowed, provided there is no bleeding, no midline shift, no need for steroids or anti-convulsants, and no symptoms
* Must agree to obtain residual tumor tissue available from the existing diagnostic biopsy tumor tissue
* Eastern cooperative oncology group (ECOG) performance status (PS) 0-1 OR Karnofsky PS 60-100%
* Life expectancy \> 12 weeks
* White blood cell (WBC) \>= 3,000/mm\^3
* Absolute neutrophil count \>= 1,500/mm\^3
* Bilirubin =\< 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and ALT =\< 2.5 times ULN
* Creatinine =\< 3 times ULN OR Creatinine clearance \>= 60 mL/min
* No uncontrolled congestive heart failure or potentially life-threatening arrhythmia
* No angina at rest
* No neuropathy \>= grade 2
* No chronic diarrhea or history of inflammatory bowel disease
* No history of pulmonary fibrosis (other than in an irradiated field)
* No other concurrent serious medical illness
* O2 saturation \> 92% on room air
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No history of allergic reactions to compounds of similar chemical or biological composition to dasatinib
* No heart rate-corrected QT interval (QTc) prolongation (i.e., QTC \>= 480 msec) or other significant ECG abnormalities that could lead to adverse effects if the QTc interval were prolonged
* No medical condition that impairs the ability to swallow, retain, or absorb dasatinib including, but not limited to, any of the following:

  * Gastrointestinal tract disease resulting in an inability to take oral medication, requirement for IV alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease
* No myocardial infarction or ventricular tachyarrhythmia within the past 6 months
* left ventricular ejection fraction (LVEF) normal
* No major conduction abnormality (unless cardiac pacemaker is present)
* No ongoing or active infection
* No history of significant bleeding disorder (congenital \[von Willebrand's disease\] or acquired \[antifactor VIII antibodies\])
* No psychiatric illness or social situation that would preclude study compliance
* No prior chemotherapy or biologic therapy for recurrent or metastatic non-small cell lung cancer
* Adjuvant cytotoxic chemotherapy after surgical resection or chemotherapy with radiation for locally advanced disease (curative intent) allowed provided disease recurrence \>= 3 months after completion of last chemotherapy dose
* Measurable disease must be outside the radiotherapy port OR clearly growing inside the port
* No prior radiotherapy to \>= 25% of the marrow-containing skeleton
* At least 7 days since prior and no concurrent medications that are inhibitors or inducers of CYP3A4
* At least 7 days since prior and no concurrent agents with proarrhythmic potential
* No other concurrent investigational agents
* No other concurrent anticancer agents or therapies
* No concurrent antiretroviral therapy for HIV-positive patients
* No concurrent systemic antacids (H2 receptor antagonists and proton pump inhibitors)
* Locally acting antacids allowed except for 2 hours before and after dasatinib administration

Primary outcomes:
measure: Number of Participants With Objective Response (Complete Response (CR) or Partial Response (PR))
timeFrame: 12 weeks
measure: Progression-free Survival (PFS)
timeFrame: Time from start of treatment to time of progression or death, assessed at 2 months
Secondary outcomes:
Other outcomes:
measure: Time to Progression (TTP)
timeFrame: Time from start of treatment to time of progression or death, assessed radiographically every 6 weeks
measure: Epidermal Growth Factor Receptor (EGFR) Mutational Status
timeFrame: Baseline
measure: Epidermal Growth Factor Receptor (EGFR) Copy Number
timeFrame: Baseline
measure: Phospho-Src (pSrc) Expression
timeFrame: Baseline
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Faye Johnson
role: PRINCIPAL_INVESTIGATOR
References: