Letrozole in Uterine Leiomyosarcoma

Study Overview
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Brief Summary
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This is a clinical trial to test letrozole in patients with uterine leiomyosarcoma. The main question is will treatment with letrozole extend progression-free survival in patients. Patients will receive 2/5 mg of letrozole daily.

Detailed Description
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This is a randomized phase II study of letrozole (Femara) administered 2.5 mg orally daily to patients with newly diagnosed clinical stage I and II LMS. Using an adaptive randomization, patients will be assigned to either the treatment arm (letrozole group) or observation. The primary outcome for this trial is the time to progression.

Official Title
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A Randomized Phase II Study of Letrozole Versus Observation in Patients With Newly Diagnosed Uterine Leiomyosarcoma

Conditions
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Uterine Leiomyosarcoma

Intervention / Treatment
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* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have histologically confirmed uterine leiomyosarcoma with disease limited to the uterus (FIGO stage 1 or 2). Tumors must express ER positivity by immunohistochemistry (ER expression greater than or equal to 10% by immunohistochemistry). Must have completed hysterectomy and bilateral salpingo-oopherectomy no more than 12 weeks from initiation of therapy All patients must have no measurable disease within 6 weeks of initiation of therapy. Measurable disease is defined by RECIST version 1.1. Patient must be able to swallow oral medications. Patient must have an ECOG performance status of 0 to 2. Patients must have adequate organ and marrow function as defined below NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower limit of normal = LLN Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1500/mcl Platelets greater than or equal to 100,000 cells/mcl Hemoglobin greater than or equal to 8 g/dL (Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after erythrocyte transfusion). Renal function: Creatinine less than or equal to 1.5 x ULN Hepatic function: Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are permitted). ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or equal to 3 x ULN Alkaline phosphatase less than or equal to 2.5 x ULN Albumin greater than or equal to 2.8 g/dL Patients must have signed an approved informed consent and authorization permitting release of personal health information. Patients must be at least 18 years of age. Exclusion Criteria: Patients who have a history of taking any aromatase inhibitor. Patients who do not have pure uterine sarcomas (i.e., no mixed malignant mullerian tumors). Patients with active or uncontrolled systemic infection Patients with concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past two years. Patients are also excluded if their previous cancer treatment contraindicates this protocol. Patients who are pregnant or breast-feeding. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 30 days prior to dosing. Patients with any other severe concurrent disease, which would make the patient inappropriate for entry into this study, including significant hepatic, renal, or gastrointestinal diseases. Patients with history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with an ejection fraction under 40%. Patients currently receiving chemotherapy or radiation therapy. Patients with duodenal stent or other GI disorder/defect that would interfere with absorption of oral medication Patients deemed otherwise clinically unfit for clinical trial per investigators discretion

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole<br>Letrozole 2.5 mg orally | Drug: Letrozole<br>* Letrozole 2.5 mg PO daily<br>|
| No Intervention: Observation<br>Observation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | Measured from time of enrollment until date of progression or death up 3 years from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | Measured for time of enrollment to time of death assessed up to 5 years from randomization |