Saracatinib in Treating Patients With Relapsed or Refractory Thymoma or Thymic Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well saracatinib works in treating patients with relapsed or refractory thymoma or thymic cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the objective response rate (complete response and partial response) in patients with relapsed or refractory thymoma or thymic carcinoma treated with AZD0530. SECONDARY OBJECTIVES: I. To evaluate the toxicity of AZD0530 in these patients. II. To evaluate the progression-free survival of these patients. III. To evaluate the overall survival of these patients. IV. To evaluate the disease control rate, defined as complete response, partial response, and stable disease, in these patients. OUTLINE: This is a multicenter study. Patients receive oral saracatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.

Official Title
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Phase II Trial of AZD0530 for Patients With Relapsed/Refractory Thymic Malignancies (Thymoma and Thymic Carcinoma)

Conditions
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Invasive Thymoma and Thymic Carcinoma, Recurrent Thymoma and Thymic Carcinoma, Stage III Thymoma, Stage IVA Thymoma, Stage IVB Thymoma

Intervention / Treatment
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* Drug: saracatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive thymoma or thymic carcinoma, meeting the following criteria: Relapsed or refractory disease Metastatic, unresectable disease Locally invasive disease allowed provided it is not resectable and has been previously treated Progressive disease Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan Must have received >= 1 prior chemotherapy regimen No active brain metastases Patients with previously treated brain metastases (surgical resection or radiotherapy) are eligible provided they have documented stable brain disease for >= 1 month after completion of therapy and are asymptomatic ECOG performance status 0-2 Leukocytes >= 3,000/mm^3 ANC >= 1,500/mm^3 Platelet count >= 100,000/mm^3 Hemoglobin > 9 g/dL Serum bilirubin < 2.0 times upper limit of normal (ULN) Transaminases =< 2.5 times ULN (< 5.0 times ULN if liver metastasis is present) Serum creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min Urine protein:creatinine ratio < 0.5 OR urine protein < 1,000 mg by 24-hour urine collection QTc < 460 msec Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after completion of study treatment No known history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530 No other malignancies within the past 3 years, except curatively treated in situ carcinoma of the cervix or completely resected nonmelanoma skin cancer No concurrent active malignancies other than thymic malignancy No condition that impairs the ability to swallow AZD0350 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) No cardiac dysfunction including, but not limited to, any of the following: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia History of ischemic heart disease Myocardial infarction within the past year No QTc prolongation or other significant ECG abnormalities No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg) No evidence of severe or uncontrolled systemic conditions that would make it undesirable to participate in the study or that would jeopardize compliance with the study, including any of the following: Severe hepatic impairment Interstitial lung disease (bilateral, diffuse, or parenchymal lung disease) Unstable or uncompensated respiratory condition Unstable or uncompensated cardiac condition No uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Mental health issues or social circumstances that would limit compliance with study requirements No prior src inhibitors At least 4 weeks since prior systemic therapy (6 weeks for carmustine or mitomycin C) At least 8 weeks since prior immunotherapy At least 4 weeks since prior octreotide Concurrent octreotide for pure red cell aplasia allowed provided patient continues on the same dose and schedule, has had a response to this drug, and has demonstrated progressive thymoma by radiography or physical exam At least 4 weeks since prior surgery and recovered At least 4 weeks since prior investigational agents At least 4 weeks since prior radiotherapy to measurable disease sites (2 weeks for palliative radiotherapy to metastatic sites) and recovered At least 7 days since prior and no concurrent active CYP3A4 agents or substances No other concurrent investigational or anticancer agents No concurrent combination antiretroviral therapy for HIV-positive patients Concurrent steroids allowed for treatment of a pre-existing autoimmune disorder or as antiemetic 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: Arm I<br>Patients receive oral saracatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 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 |
| --- | --- | --- |
| Objective Response Rate (Complete and Partial Response) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The objective response rate will be reported by each disease classification. The percent of patients having an objective response (complete or partial response) will be estimated with a 95% exact binomial confidence interval for the percent of patients receiving drug. Note: there were no objective responses in this trial. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This will be examined in an exploratory fashion using Kaplan-Meier estimates. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis. | Time from the date of registration to the first reported outcome event, assessed up to 5 years | 
| Overall Survival | Will be examined in an exploratory fashion using Kaplan-Meier estimates. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis. | Time from the date of registration to last reported date of survival, assessed up to 5 years | 
| Disease Control Rate | Will be examined in an exploratory fashion using Kaplan-Meier estimates. Disease control rate defined as complete response (CR) + partial response (PR) + stable disease (SD). The length of time until progression or until last evaluation will be calculated. For patients who did not progress, they will be censored in the analysis. | Up to 5 years | 
| Expected Toxicities Including Skin Rashes and Diarrhea | Number of patients who had toxicities classified as skin rashes and diarrhea within the adverse events. | Up to 5 years |