Aromatase Inhibitor Host Factors Study

Study Overview
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Brief Summary
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The purpose of this study is to examine how key patient factors, including body size affect how well letrozole suppresses circulating estrogen levels. This study has two components: (1) Part A - an observational phase to evaluate the impact of vitamin D and obesity on estrogen suppression in post-menopausal women already receiving letrozole treatment, and (2) Part B - an interventional phase for women with body mass index (BMI) > 25 kg/m2 to assess the effect of double AI dose on estrogen levels. If BMI or other patient factors reduce the effectiveness of letrozole, modifications to treatment recommendations and studies to test higher dosing of letrozole may be needed to maximize the benefit of this treatment and minimize the risk of the breast cancer coming back.

Detailed Description
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The available evidence suggests that circulating estradiol levels play a critical role in determining effectiveness of aromatase inhibitor therapy, and that maximal suppression of aromatase activity and estrogen production is essential for optimal disease control. Host factors such as high 25-Hydroxy Vitamin D (25-OH D) levels and obesity, which might increase residual estrogen levels, could adversely impact outcome and lead to an increased risk of recurrence or death. The primary objective of Part A (which includes women regardless of BMI) is to directly evaluate the relationship between (i) 25-OH D levels and serum estrogen levels and (ii) BMI and serum estrogen levels in a cohort of postmenopausal women on standard dose letrozole therapy (2.5 mg/day). Part B (which includes only women with BMI > 25 kg/m2) will determine whether an increased dose of letrozole (5 mg/day), which had no dose limiting side effects in a Phase I study improves suppression of estrogen in overweight/obese women.

Official Title
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Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal female patients histological confirmed diagnosis of estrogen receptor and/or progesterone receptor positive breast cancer (Stage I-III) who have completed local therapy Currently prescribed and taking letrozole 2.5 mg daily for a minimum of 3 months Willing to provide written informed consent to participate for the experimental arm: all of the above and body mass index (BMI) > 25 kg/m2 Exclusion Criteria: Known abnormal liver or renal function defined by: Serum Creatinine > 1.25 times institutional upper limit of normal (ULN) or Calculated Creatinine Clearance < 40 mL/min Serum Bilirubin, Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 times ULN Presence of persistent local or known metastatic cancer
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 |
| --- | --- |
| Other: Post-menopausal Women Using Adjuvant Letrozole<br>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants | Drug: Letrozole<br>* Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A Correlation of Day 29 Estradiol With BMI | Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI | Day 29 | 
| Part A Correlation of Day 29 Estrone With BMI | Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI | Day 29 | 
| Part A Correlation of Day 29 Estradiol With Vitamin D | Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level | Day 29 | 
| Part A Correlation of Day 29 Estrone With Vitamin D | Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level | Day 29 | 
| Part B Change in Estradiol Level After Double Dose of Letrozole | In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole | Day 29 to Day 58 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Letrozole |  | Day 29 and day 58 | 
| Endocrine Symptoms During Part A of Study | Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life | baseline, day 29 (end of part A) | 
| Endocrine Symptoms During Part B of the Study | Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life | day 29 (end of part A) and day 58 (end of part B) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aromatase Inhibitors