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Aromatase Inhibitor Host Factors Study

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ClinicalTrials.gov Identifier: NCT01669343
Recruitment Status : Completed
First Posted : August 21, 2012
Results First Posted : May 13, 2021
Last Update Posted : May 13, 2021
Sponsor:
Information provided by (Responsible Party):
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

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.


Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Letrozole Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 121 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole
Actual Study Start Date : October 2012
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Letrozole

Arm Intervention/treatment
Post-menopausal Women Using Adjuvant Letrozole
Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants
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.
Other Name: Femara




Primary Outcome Measures :
  1. Part A Correlation of Day 29 Estradiol With BMI [ Time Frame: Day 29 ]
    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

  2. Part A Correlation of Day 29 Estrone With BMI [ Time Frame: Day 29 ]
    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

  3. Part A Correlation of Day 29 Estradiol With Vitamin D [ Time Frame: Day 29 ]
    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

  4. Part A Correlation of Day 29 Estrone With Vitamin D [ Time Frame: Day 29 ]
    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

  5. Part B Change in Estradiol Level After Double Dose of Letrozole [ Time Frame: Day 29 to Day 58 ]
    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


Secondary Outcome Measures :
  1. Plasma Letrozole [ Time Frame: Day 29 and day 58 ]
  2. Endocrine Symptoms During Part A of Study [ Time Frame: baseline, day 29 (end of part A) ]
    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

  3. Endocrine Symptoms During Part B of the Study [ Time Frame: day 29 (end of part A) and day 58 (end of part B) ]
    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


Other Outcome Measures:
  1. Musculoskeletal Symptoms [ Time Frame: baseline (day 1), day 29 (end of part A) and day 58 (end of part B) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01669343


Locations
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Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 1M9
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Women's College Hospital
Toronto, Ontario, Canada, M5S 1B1
Sponsors and Collaborators
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Investigators
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Principal Investigator: Srikala Sridhar, M.D. Princess Margaret Hospital, Canada
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Responsible Party: Samuel Lunenfeld Research Institute, Mount Sinai Hospital
ClinicalTrials.gov Identifier: NCT01669343    
Other Study ID Numbers: AI Host Factors
First Posted: August 21, 2012    Key Record Dates
Results First Posted: May 13, 2021
Last Update Posted: May 13, 2021
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The data supporting the related manuscript are kept in institutional file storage on an internal server at Lunenfeld-Tanenbaum Research Institute. There are de-identification concerns in small, regionally restricted, clinical datasets which prevent these data being openly available, but data will be made available at reasonable request from the corresponding author for up to and including 5 years from publication of the related manuscript.

For all data requests please contact:

Dr David Cescon, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Dave.Cescon@uhn.ca

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Up to and including 5 years from publication of the related manuscript (Elliott, Mitchell J et al. "Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study." NPJ breast cancer vol. 6 22. 12 Jun. 2020)
Access Criteria: Reasonable request
Keywords provided by Samuel Lunenfeld Research Institute, Mount Sinai Hospital:
Aromatase Inhibitors
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs