Dasatinib in Treating Patients With Relapsed Small Cell Lung Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well dasatinib works in treating patients with relapse small cell lung cancer. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVE I. Determine the efficacy of dasatinib in patients with relapsed small cell lung cancer. SECONDARY OBJECTIVE II. Determine the objective response rate (complete and partial response) in patients treated with this drug. III. Determine the overall survival of patients treated with this drug. IV. Determine the toxicity of this drug in these patients. OUTLINE: Patients receive oral dasatinib twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at least every 3 months for 1 year and then every 6 months for 3 years.

Official Title
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A Phase II Study of Dasatinib (NSC #732517) in Patients With Chemo-Sensitive Relapsed Small Cell Lung Cancer

Conditions
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Extensive Stage Small Cell Lung Cancer, Limited Stage Small Cell Lung Cancer, Recurrent Small Cell Lung Cancer

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed small cell lung cancer (SCLC) (limited or extensive stage disease) Progressive or recurrent disease after an initial response to first-line treatment with a platinum-based chemotherapy with or without concurrent definitive radiotherapy to the chest (chemotherapy must have been completed at least 90 days prior to documentation of relapse) Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan Lesions that are not considered measurable include the following: Bone lesions Leptomeningeal disease Ascites Pleural or pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area, unless progression after radiotherapy is documented in these lesions No known brain metastases (previously treated brain metastases allowed provided they are neurologically stable for >= 4 weeks) ECOG performance status 0-1 Platelet count >= 100,000/mm^3 Bilirubin =< 1.5 times upper limit of normal (ULN) Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min AST =< 2.5 times ULN Not pregnant or nursing Negative pregnancy test No significant cardiac disease, including any of the following: New York Heart Association class III-IV heart disease Myocardial infarction or ventricular tachyarrhythmia within the past 6 months Prolonged QTc > 480 msec (Fridericia correction) Major conduction abnormality (unless a cardiac pacemaker is present) No more than 1 prior chemotherapy regimen No prior dasatinib or compounds of similar chemical composition or similar biologic therapeutic activity including, but not limited to, any inhibitors of SRC, BCR-ABL, c-KIT, EPHA2, or PDGFRB kinases At least 2 weeks since prior definitive or palliative radiotherapy (prior radiotherapy allowed in the context of combined modality treatment with curative intent for limited stage disease; prophylactic cranial radiotherapy; or palliative radiotherapy initially or at relapse) At least 2 weeks since prior surgery and recovered At least 1 week since prior and no concurrent agents with proarrhythmic potential At least 1 week since prior and no concurrent CYP3A4 inhibitors or inducers At least 1 week since prior and no concurrent grapefruit concentrate No concurrent palliative radiotherapy No concurrent hormones or other chemotherapeutic agents, except steroids for adrenal failure, hormones for noncancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent chemotherapeutic or investigational agents Fertile patients must use effective contraception during and for >= 6 weeks after completion of study therapy

Ages Eligible for Study
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Minimum Age: 18 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: Treatment (dasatinib)<br>Patients receive oral dasatinib twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: dasatinib<br>* Given PO<br>* Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Week Progression Free Survival | Percentage of patients who were alive and progression free at 6-weeks. The 6-week progression free survival was estimated using the Kaplan Meier method. Progressive Disease was defined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria as 20% increase in sum of longest diameter of target lesions. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure. | Time from registration to progression (up to 3 years) | 
| Response to Therapy | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. | Assessed every 2 cycles (up to 3 years) | 
| Overall Survival | Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method. | Time from registration to death (up to 3 years) | 
| Number of Participants With Grade 3 or Higher Adverse Events | The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 was used to evaluate toxicity. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death. | Assessed during treatment |