AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II study is studying how well giving AZD0530 works in treating patients with extensive-stage small cell lung cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the 12-week progression-free survival rate of patients with extensive stage small cell lung cancer treated with AZD0530. SECONDARY OBJECTIVES: I. To determine the response rate in patients treated with this drug. II. To determine the overall survival and time-to-progression in patients treated with this drug. III. To determine the adverse events of AZD0530 in these patients IV. To determine the effect of AZD0530 treatment on levels of circulating tumor cells in these patients. V. To determine potential predictive markers of response in circulating tumor cells after treatment with this drug. VI. To evaluate the rate of tumor marker (i.e., circulating tumor cells) stabilization in patients treated with this drug. TERTIARY OBJECTIVES: I. To determine the effect of AZD0530 treatment on levels of circulating tumor cells. II. To determine potential predictive markers of response in circulating tumor cells after treatment with this drug. III. To evaluate the rate of tumor marker (i.e., circulating tumor cells) stabilization in patients treated with this drug. OUTLINE: Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are obtained at baseline and periodically during study to determine levels of circulating tumor cells for defined translational studies. After completion of study therapy, patients are followed periodically for up to 2 years.

Official Title
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Phase II Study of the c-SRC Inhibitor AZD0530 After Four Cycles of Cytoreductive Chemotherapy for Patients With Extensive Stage Small Cell Lung Carcinoma

Conditions
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Extensive Stage Small Cell Lung Cancer, Lung Metastases, Malignant Pleural Effusion, Recurrent Small Cell Lung Cancer

Intervention / Treatment
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* Drug: saracatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed small cell lung cancer No mixed histology Extensive stage disease, defined as any of the following: Metastatic disease outside the chest Contralateral supraclavicular nodes or contralateral hilar nodes that cannot be included in a single radiation port Cytologically confirmed malignant pleural effusion Clinically significant effusions (e.g., symptomatic pleural effusion) must be drained prior to treatment Previously untreated disease* OR stable disease, partial response, or complete response ≤ 4 weeks after completion of one course (four 3-week courses) of standard platinum-based chemotherapy No symptomatic, untreated, or uncontrolled CNS metastases CNS metastases previously treated with whole brain radiotherapy allowed ECOG performance status (PS) 0-2 Life expectancy ≥ 12 weeks WBC ≥ 3,000/mm³ ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin > 9.0 g/dL Total bilirubin < 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN ALT and AST ≤ 3 times ULN (≤ 5 times ULN if liver involvement) Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min Proteinuria ≤ +1 on two consecutive dipsticks taken no less than 24hours apart Not pregnant or nursing Negative pregnancy test Fertile patients must use effective protection during and for up to 8 weeks after completion of study therapy QTc interval ≤ 460 msec No seizure disorder No significant traumatic injury ≤ 4 weeks prior to registration No clinically significant infection No HIV-positivity No second primary malignancy, except for carcinoma in situ of the cervix or nonmelanoma skin cancer, unless prior malignancy was diagnosed and treated ≥ 5 years with no subsequent evidence of recurrence Patients with a history of low grade(Gleason score ≤ 6) localized prostate cancer will be eligible even if diagnosed < 5 years prior to registration No concurrent severe and/or uncontrolled medical conditions, including any of the following: Cardiac arrhythmias Angina pectoris uncontrolled with medication Myocardial infarction within the past 3 months Significant ECG abnormalities Hypertension, labile hypertension, or history of poor compliance with anti-hypertensive medication Congestive heart failure within the past 3 months, unless ejection fraction > 40% Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the lung Poorly controlled diabetes No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530 No condition that impairs the ability to swallow AZD0530 tablets, including any of the following: Gastrointestinal tract disease resulting in an inability to take oral medication or requiring IV alimentation Prior surgical procedures affecting absorption of AZD0530 tablets Active peptic ulcer disease No serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study At least 4 weeks since prior major surgery (i.e., laparotomy) or open biopsy At least 2 weeks since prior minor surgery At least 4 weeks since any prior investigational ancillary therapy (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation) At least 7 days since prior use of strong inhibitors of CYP3A4 and no concurrent use for up to 7 days after discontinuation of AZD0530 Prior nonthoracic palliative radiotherapy allowed Concurrent bisphosphonates for treatment of lytic metastatic bone disease allowed at the discretion of the treating physician No concurrent prophylactic granulocyte colony-stimulating factor (i.e., G-CSF) No concurrent products that stimulate thrombopoiesis No concurrent St. John's wort No other concurrent chemotherapy, immunotherapy, hormonal therapy,or radiotherapy

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 (saracatinib)<br>Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are obtained at baseline and periodically during study to determine levels of circulating tumor cells for defined translational studies. | Drug: saracatinib<br>* Given orally<br>* Other names: AZD0530;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Rate at 12 Weeks | The progression-free survival (PFS) rate at 12 weeks will be estimated by calculating the number of patients that are alive and progression-free at 12 weeks post-registration divided by the total number of evaluable patients and multiplied by 100. All patients meeting the eligibility criteria who have signed a consent form, begun AZD0530 treatment, and are not lost to follow-up before 12 weeks, will be considered evaluable for the 12-week progression-free survival (PFS) rate. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is defined as having a new lesion or having at least a 20% increase in the sum of the longest diameter of target lesions from baseline. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. | From registration to death due to any cause, assessed up to 2 years | 
| Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart) | Response was assessed using the RECIST v1.1 criteria. Patients were evaluated after every other cycle (after cycle 2, 4, 6, etc...) and when progression is suspected. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart.. | After every other 21-day cycle, up to 2 years. | 
| Progression Free Survival | Progression Free Survival (PFS) is defined as the time from registration to documentation of disease progression or death, whichever occurs first. The distribution of time to progression will be estimated using the method of Kaplan-Meier. | From registration to documentation of disease progression or death, assessed up to 2 years |