Clinical trial NCT01669343: Aromatase Inhibitor Host Factors Study
Official title: Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Neoplasms
Keywords: Aromatase Inhibitors
Lead sponsor: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Sponsor class: OTHER
First posted: 2012-08-21
Enrollment: 121
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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:

  1. Serum Creatinine \> 1.25 times institutional upper limit of normal (ULN) or Calculated Creatinine Clearance \< 40 mL/min
  2. Serum Bilirubin, Aspartate transaminase (AST) or alanine transaminase (ALT) \> 1.5 times ULN
* Presence of persistent local or known metastatic cancer

Primary outcomes:
measure: Part A Correlation of Day 29 Estradiol With BMI
timeFrame: Day 29
measure: Part A Correlation of Day 29 Estrone With BMI
timeFrame: Day 29
measure: Part A Correlation of Day 29 Estradiol With Vitamin D
timeFrame: Day 29
measure: Part A Correlation of Day 29 Estrone With Vitamin D
timeFrame: Day 29
measure: Part B Change in Estradiol Level After Double Dose of Letrozole
timeFrame: Day 29 to Day 58
Secondary outcomes:
measure: Plasma Letrozole
timeFrame: Day 29 and day 58
measure: Endocrine Symptoms During Part A of Study
timeFrame: baseline, day 29 (end of part A)
measure: Endocrine Symptoms During Part B of the Study
timeFrame: day 29 (end of part A) and day 58 (end of part B)
Other outcomes:
measure: Musculoskeletal Symptoms
timeFrame: baseline (day 1), day 29 (end of part A) and day 58 (end of part B)
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Women's College Hospital
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Srikala Sridhar, M.D.
role: PRINCIPAL_INVESTIGATOR
References: