A Randomized Phase II Study of Letrozole Versus Observation in Patients with Newly Diagnosed Uterine Leiomyosarcoma

L
Lisa Landrum, MD, PhD, MS

Primary Investigator

Enrolling By Invitation
18 years - 100 years
Female
Phase 2
2 Locations

Brief description of study

What is the purpose of this study?
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.
 
Translational Objectives: 
1. To preliminarily assess IHC hormone receptor expression and correlation to response to letrozole in uterine leiomyosarcoma.
2. To evaluate gene expression signatures of hormone receptor activity, tumor biology, and tumor microenvironment in relation to response to letrozole in uterine leiomyosarcoma. 3. To evaluate the contribution of single nucleotide polymorphism rs3820282 to tumor biology and response to letrozole in uterine leiomyosarcoma.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632</div>

Detailed description of study

What will happen during the study?

  • 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.Primary Objective: To measure progression free survival (PFS) with the use of letrozole in women with Stage I estrogen receptor (ER) positive uterine leiomyosarcoma.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Uterine Leiomyosarcoma
  • Age: 18 years - 100 years
  • Gender: Female

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

Updated on 23 Jan 2025. Study ID: CTO-GOG-3088, 24154
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