Dasatinib in Treating Patients With Advanced Lung Cancer That Is No Longer Responding to Erlotinib or Gefitinib

Study Overview
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Brief Summary
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RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with advanced lung cancer that is no longer responding to erlotinib or gefitinib.

Detailed Description
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OBJECTIVES: Primary To determine the overall response rate (complete response and partial response) in patients with acquired erlotinib hydrochloride- or gefitinib-resistant advanced adenocarcinoma of the lung treated with dasatinib. Secondary To determine the progression-free survival and overall survival of patients treated with this drug. To determine the overall response rate in patients with EGFR T790M lung adenocarcinomas treated with this drug. To determine the progression-free survival and overall survival of patients with EGFR T790M lung adenocarcinomas treated with this drug. To determine the toxicity profile of dasatinib in these patients. OUTLINE: Beginning 1 week after completion of erlotinib hydrochloride or gefitinib therapy, patients receive oral dasatinib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Response is assessed by CT scan at 4 weeks, 8 weeks, and then every 8 weeks thereafter.

Official Title
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A Phase 2 Trial of Dasatinib in Patients With Lung Adenocarcinoma With Acquired Resistance to Erlotinib or Gefitinib

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed adenocarcinoma of the lung Advanced disease Previously treated with erlotinib hydrochloride or gefitinib for 6 months (at any time) and meets 1 of the following criteria: Previously received treatment with erlotinib hydrochloride or gefitinib* and had a radiographic partial or complete response to treatment with erlotinib hydrochloride or gefitinib as defined by RECIST or WHO criteria Documented mutation in EGFR from tumor DNA NOTE: *Patients may have received other treatments subsequently including radiation or chemotherapy Must have developed acquired resistance to erlotinib hydrochloride or gefitinib Radiographic evidence of disease progression during treatment with erlotinib hydrochloride or gefitinib Have previously undergone a biopsy of a site of progressive disease on protocol MSKCC 04-103* NOTE: *Results of this biopsy are not required to be enrolled on this trial Measurable indicator lesions have not been previously irradiated No CNS lesion that is symptomatic and/or requiring escalating doses of corticosteroids PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% WBC ≥ 3,000/mm³ Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/mm³ Total bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2.5 times upper limit of normal Creatinine ≤ 2 mg/dL or creatinine clearance ≥ 55 mL/min QTc < 450 msec Able to take oral medications Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 4 weeks after study drug is stopped No significant medical history or unstable medical condition, including any of the following: History of diagnosed congenital long QT syndrome Ventricular arrhythmia Congestive heart failure Recent myocardial infarction Unstable angina Active infection Uncontrolled hypertension PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior cytotoxic chemotherapy At least 3 weeks since prior radiation therapy to a major bone-marrow containing area At least 7 days since prior quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, or lidoflazine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib<br>Beginning 1 week after completion of erlotinib hydrochloride or gefitinib therapy, patients receive oral dasatinib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Response is assessed by CT scan at 4 weeks, 8 weeks, and then every 8 weeks thereafter. | Drug: dasatinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Overall Objective Response | To determine the overall response rate in patients with acquired erlotinib hydrochloride- or gefitinibresistant advanced adenocarcinoma of the lung treated with dasatinib using the RECIST criteria. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.22 Changes in only the largest diameter (uni-dimensional measurement) of the tumor lesions are used in the RECIST. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the lung, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer