AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma

Study Overview
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Brief Summary
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This phase II trial is studying how well AZD0530 works in treating patients with recurrent locally advanced, or metastatic soft tissue sarcoma. AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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OBJECTIVES: I. To assess the efficacy of AZD0530, in terms of disease control rate (i.e., response rate and stable disease rate), in patients with recurrent locally advanced or metastatic soft tissue sarcoma. II. To assess the toxicity, time to progression, and response duration of AZD0530 in these patients. OUTLINE: This is a multicenter study. Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 8 weeks.

Official Title
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A Phase 2 Study of AZD0530 in Recurrent or Metastatic Soft Tissue Sarcoma

Conditions
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Adult Fibrosarcoma, Adult Leiomyosarcoma, Adult Liposarcoma, Adult Malignant Fibrous Histiocytoma, Adult Rhabdomyosarcoma, Dermatofibrosarcoma Protuberans, Endometrial Stromal Sarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Uterine Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage III Uterine Sarcoma, Stage IV Adult Soft Tissue Sarcoma, Stage IV Uterine Sarcoma, Uterine Carcinosarcoma, Uterine Leiomyosarcoma

Intervention / Treatment
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* Drug: saracatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Leukocytes >= 3,000/mcL Histologically or cytologically confirmed soft tissue sarcoma including, but not limited to any of: Malignant fibrous histiocytoma Fibrosarcoma - non infantile Leiomyosarcoma - not uterine Liposarcoma Non-rhabdomyosarcoma soft tissue sarcoma Rhabdomyosarcoma, not otherwise specified Carcinosarcoma of the uterus Dermatofibrosarcoma Endometrial stromal sarcoma Leiomyosarcoma - uterus Recurrent or locally advanced or metastatic disease No more than two prior lines of chemotherapy for metastatic disease (not including adjuvant chemotherapy) Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan Target measurable lesion must not have been in previous radiation portal, unless progression of this lesion after radiotherapy has been documented ECOG performance status (PS) 0-2 or Karnofsky PS 60-100% Life expectancy > 12 weeks Recovered from all prior therapy Platelet count >= 100,000/mcL Hemoglobin > 9 g/dL Total bilirubin =< 1.25 times upper limit of normal (ULN) AST and ALT =< 3 times ULN Creatinine =< 1.5 times ULN OR creatinine clearance >= 50 mL/min Urine protein:creatinine ratio =< 1.0 OR 24-hour urine protein < 1,000 mg ANC >1,500/mcL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 8 weeks after completion of study therapy No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530 No QTc prolongation (defined as a QTc interval >= to 460 msecs) or other significant ECG abnormalities No poorly controlled hypertension (i.e., systolic blood pressure (BP) >= 140 mm Hg, or diastolic BP >= 90 mm Hg) No condition that impairs a patient's ability to swallow AZD0530 tablets, including any of the following: Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation Prior surgical procedures affecting absorption Active peptic ulcer disease Exclusion Criteria: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) No intercurrent cardiac dysfunction including, but not limited to, any of the following: Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia No history of ischemic heart disease, including myocardial infarction No uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements More than 4 weeks since prior radiotherapy More than 7 days since prior and no concurrent prohibited CYP3A4-active agents or substances No other concurrent investigational agents or commercial agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients No known brain metastases

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 AZD0530 (saracatinib ) at a dose of 175 mg, once daily, 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 |
| --- | --- | --- |
| Disease Control Rate, Defined as the Number of Patients Who Achieved Complete Response, Partial Response or Stable Disease For a Period of More Than 4 Months. | Response and progression will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Changes in only the largest diameter (unidimensional measurement) of the tumor lesions; where CR is disappearance of all target lesions, PR is at least 30% decrease in the sum of longest diameter, PD is at least 20% increase in the sum of longest diameter recorded since the treatment started and SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions | Up to 5 years | 
| Overall Survival | Median was estimated. The Kaplan-Meier method will be used to estimate overall survival estimates. | Up to 5 years | 
| Stable Disease Rate | Achieved stable disease as their best response | Up to 5 years | 
| Duration of Response | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Tumor Response of more than 4 months was counted toward the Disease Control Rate. | Up to 5 years | 
| Time to Disease Progression | The Kaplan-Meier method will be used to estimate time to progression estimates. 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. | Up to 5 years |