Dasatinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

Phase 2

Completed

Conditions: Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer

Interventions: Drug: dasatinib

Registration Number: NCT00459342

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Time from start of treatment to time of progression or death, assessed at 2 months	Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death.
Number of Participants With Objective Response (Complete Response (CR) or Partial Response (PR))	12 weeks	Objective response defined as participants with Complete Response (CR) or Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RECIST definitions are Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Response measured by tumor size on computed tomography scans and by metabolic activity on positron emission tomography scans.

Secondary Outcome Measures