Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well sunitinib malate works in treating patients with endometrial cancer that has come back after a period of improvement (recurrent) or has spread to other places in the body (metastatic). 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. To assess the objective response rate of recurrent or metastatic endometrial cancer to sunitinib (sunitinib malate). II. To assess the frequency of prolonged stable disease (as defined by percentage [%] of patients alive and free from progressive disease at 6 months) in patients with recurrent or metastatic endometrial cancer treated with sunitinib. SECONDARY OBJECTIVES: I. To assess time-to- progression, median overall survival, and rate of one-year survival in patients with recurrent or metastatic endometrial cancer treated with sunitinib. II. To assess the toxicity associated with sunitinib in patients with recurrent or metastatic endometrial cancer. OUTLINE: Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After the completion of study treatment, patients are followed up at 4 weeks and then every 3 months until relapse.

Official Title
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A Phase 2 Study of Sunitinib Malate in Recurrent or Metastatic Endometrial Carcinoma

Conditions
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Uterine Carcinosarcoma, Endometrial Adenocarcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Serous Adenocarcinoma, Recurrent Uterine Corpus Carcinoma, Stage IVA Uterine Corpus Cancer AJCC v7, Stage IVB Uterine Corpus Cancer AJCC v7, Uterine Corpus Carcinosarcoma

Intervention / Treatment
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* Drug: Sunitinib Malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed endometrial cancer; adenocarcinoma (endometrioid and serous/papillary serous) and carcinosarcoma (ie. malignant mixed Mullerian tumor [MMMT]) of the uterus will be investigated; patients with other histologies (eg. squamous cell carcinoma or leiomyosarcoma) are excluded Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan; indicator lesions must not have been previously treated with surgery, radiotherapy, or radiofrequency ablation Previously treated patients must have evidence of progressive disease, either clinically or radiographically, as assessed by the investigator Eligible patients may have received no more than one prior cytotoxic chemotherapy regimen for recurrent, locally-advanced, or metastatic disease; if the prior chemotherapy was an anthracycline, they may have received no more than 6 cycles (or less than 450 mg/m^2 doxorubicin); patients must have completed any previous chemotherapy a minimum of 4 weeks (or 6 weeks if the regimen contained carmustine [BCNU] or mitomycin) prior to study registration; prior investigational treatment is permissible (as long as such treatment completed 4 weeks prior to registration) Life expectancy of greater than 3 months Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60) Leukocytes >= 3,000/mcL Absolute neutrophil count (ANC) >= 1,500/mcL Platelets >= 100,000/mcL Hemoglobin >= 100 g/dL Serum calcium =< 12.0 mg/dL (=< 3.0 mmol/L) Total serum bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Serum lipase =< 1.5 x institutional upper limit of normal Serum amylase =< 1.5 x institutional upper limit of normal Thyroid stimulating hormone (TSH)/T3/T4 within normal institutional limits Magnesium >= 0.5 mmol/L Patients must have corrected QT interval (QTc) < 500 msec The following group of patients are eligible provided they have normal baseline cardiac function (as determined by estimate of left ventricular ejection fraction [LVEF] on echocardiogram or multi-gated acquisition scan [MUGA]): Those with a history of congestive heart failure, provided they are no greater than New York Heart Association (NYHA) class I and on treatment at baseline Those with prior anthracycline exposure Those who have received prior central thoracic radiation that included the heart in the radiotherapy port Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; all women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; at least 4 weeks must have elapsed since any major surgery Patients may not be receiving any other investigational agents Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, vascular endothelial growth factor [VEGF] Trap, etc.) are ineligible History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib Patients who have a history of serious ventricular arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF] equal to or greater than 3 beats in a row), QTc prolongation (defined as a QTc interval equal to or greater than 500 msec) or other significant electrocardiogram (ECG) abnormalities are excluded Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or diastolic blood pressure of 90 mmHg or higher) are ineligible Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT) international normalized ratio (INR) is =< 1.5 Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib tablets are excluded Patients with any of the following conditions are excluded: Serious or non-healing wound, ulcer, or bone fracture History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry History of pulmonary embolism within the past 12 months Class III or IV heart failure as defined by the NYHA functional classification system Pre-existing adrenal insufficiency (primary or secondary) The eligibility of patients taking medications that are potent inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) will be determined following a review of their case by the Principal Investigator; every effort should be made to switch patients taking such agents or substances to other medications, particularly patients who are taking enzyme-inducing anticonvulsant agents Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible Patients with known brain metastases should be excluded Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections or psychiatric illness/social situations that would limit compliance with study requirements are ineligible Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with sunitinib malate Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

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 sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: Sunitinib Malate<br>* Given PO<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Objective response rate, defined as the rate of complete or partial response as defined by the Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 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; Complete Response (CR), disappearance of all target lesions. | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Prolonged Stable Disease | Described as the best response of stable disease that is maintained for atleast 6 months | Up to 7 years | 
| Overall Survival | Estimated using the Kaplan-Meier method. | Up to 7 years | 
| Number of Participants With Adverse Effects Assessed by CTCAE Version 3.0 | Number of participants that experience at east 1 adverse event while on trial, according to the CTCAE. | Up to 7 years | 
| Time to Progression | The length of time from the date of diagnosis or the start of treatment for a disease until the disease starts to get worse or spread to other parts of the body. Assessed by Kaplan and Meier method | Up to 7 years |