Aromatase Inhibitor Host Factors Study

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01669343
• Other study ID #: AI Host Factors
• Status: Completed
• Phase: N/A
• Start date: October 2012
• Est. completion date: December 2016

Study information

• Verified date: May 2017
• Source: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Letrozole
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.

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Women's College Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Musculoskeletal Symptoms		baseline (day 1), day 29 (end of part A) and day 58 (end of part B)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Plasma Letrozole		Day 29 and day 58
Secondary	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)
Secondary	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)