Sunitinib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus

Study Overview
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Brief Summary
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This phase II trial is studying how well sunitinib works in treating patients with recurrent or persistent leiomyosarcoma of the uterus. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess the activity of sunitinib malate, in terms of rate of progression-free survival for ≥ 6 months and objective tumor response, in patients with recurrent or persistent leiomyosarcoma of the uterus who have received 1 or 2 prior cytotoxic therapies. II. Determine the frequency and severity of adverse events. SECONDARY OBJECTIVES: I. Determine the duration of progression-free survival and overall survival. OUTLINE: This is a multicenter study. Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Official Title
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A Phase II Evaluation of Sunitinib Malate (Sutent®, SU11248, NCI-Supplied Agent , NSC # 736511) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus

Conditions
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Recurrent Uterine Sarcoma, Uterine Leiomyosarcoma

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed leiomyosarcoma of the uterus Recurrent or persistent disease Refractory to curative therapy or established treatments Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Ascites and pleural effusions are not considered measurable disease Must have ≥ 1 target lesion to assess response Tumors in a previously irradiated field are considered non-target lesions unless there is documented progression or biopsy-confirmed persistence ≥ 90 days after completion of radiotherapy Received at least 1 but no more than 2 prior cytotoxic regimens Initial treatment may have included high-dose chemotherapy, consolidation, or extended therapy administered after surgery or nonsurgical assessment Cytotoxic regimens may have included any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa Not a candidate for a higher priority GOG protocol No known brain metastases GOG performance status 0-2 (for patients who have received 1 prior regimen) OR GOG 0-1 (for patients who have received 2 prior regimens) Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL Creatinine ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 1.5 times ULN QTc < 500 msec LVEF normal by echocardiogram Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 1 month after completion of study treatment Patients with a pre-existing thyroid abnormality unable to maintain normal thyroid function with medication are not eligible No significant EKG abnormalities (i.e., no history of serious ventricular arrhythmia OR EKG with ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) No sensory or motor neuropathy > grade 1 No NYHA class III-IV congestive heart failure NYHA class II cardiac dysfunction allowed History of NYHA class II heart failure that is asymptomatic on treatment allowed No active infection requiring antibiotics No other invasive malignancies within the past 5 years except for nonmelanoma skin cancer No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) No gastrointestinal tract disease resulting in an inability to take oral medication No requirement for IV alimentation No active peptic ulcer disease No other condition that would impair ability to swallow and retain study drug No serious or nonhealing wound, ulcer, or bone fracture No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days No cerebrovascular accident or transient ischemic attack within the past year No myocardial infarction, cardiac arrhythmia, stable or unstable angina, or symptomatic congestive heart failure within the past year No pulmonary embolism within the past year No uncontrolled illness including, but not limited to, any of the following: Ongoing or active infections Psychiatric illness or social situations that would preclude study compliance Recovered from prior surgery, chemotherapy, or radiotherapy Prior anthracycline exposure and central thoracic radiation that included the heart allowed provided patient has New York Heart Association (NYHA) class II cardiac function At least 1 week since prior hormonal therapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) or radiotherapy At least 4 weeks since prior major surgery At least 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin and no recurrent or metastatic disease At least 3 years since prior adjuvant chemotherapy for localized cancer of the breast and no recurrent or metastatic disease No prior radiotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma No prior chemotherapy to any portion of the abdominal cavity or pelvis unless for treatment of leiomyosarcoma No prior noncytotoxic chemotherapy for recurrent or persistent disease No prior surgical procedures affecting absorption No coronary or peripheral artery bypass graft or stenting within the past year No other prior antiangiogenic agents (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or vascular endothelial growth factor [VEGF] Trap) No other prior cancer treatment that would preclude study treatment At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following: Azole fungals (e.g., ketoconazole or itraconazole) Clarithromycin Erythromycin Diltiazem Verapamil HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir) Delavirdine At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: Rifampin Rifabutin Carbamazepine Phenobarbital Phenytoin Hypericum perforatum (St. John's wort) Efavirenz Tipranavir No concurrent proarrhythmic potential agent, including any of the following: Terfenadine Quinidine Procainamide Disopyramide Sotalol Probucol Bepridil Haloperidol Risperidone Indapamide Flecainide No concurrent therapeutic coumarin-derivative anticoagulants, such as warfarin Doses ≤ 2 mg daily allowed for prophylaxis of thrombosis Low molecular weight heparin allowed provided PT INR ≤ 1.5 No concurrent amifostine or other protective agents No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer agents or therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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 (sunitinib malate)<br>Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. | Drug: sunitinib malate<br>* Given orally<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | From study entry until disease progression, death or date of last contact., assessed up to 6 months | 
| Objective tumor response according to GOG RECIST criteria |  | Up to 5 years | 
| Frequency and severity of adverse events as assessed by CTCAE v 3.0 | The frequency and severity of all toxicities will be tabulated. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of progression-free survival | Characterized graphically and using descriptive statistics such as median survival. | Up to 5 years | 
| Duration of overall survival | Characterized graphically and using descriptive statistics such as median survival. | From entry into the study to death or the date of last contact, assessed up to 5 years |