An interventional study of Letrozole in Breast Neoplasms, sponsored by Samuel Lunenfeld Research Institute, Mount Sinai Hospital. Completed at 3 sites in Canada. Open to female participants. Per ClinicalTrials.gov, last updated 2021-05-13.
Sponsored by Samuel Lunenfeld Research Institute, Mount Sinai Hospital · Not applicable, Interventional, and Treatment
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 121 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Samuel Lunenfeld Research Institute, Mount Sinai Hospital is the lead sponsor of 135 studies on the registry; 17 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Known abnormal liver or renal function defined by:
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.
Also known as: Femara
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 29 to Day 58
Plasma Letrozole
Time frame: 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
Time frame: 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
Time frame: day 29 (end of part A) and day 58 (end of part B)
Musculoskeletal Symptoms
Time frame: baseline (day 1), day 29 (end of part A) and day 58 (end of part B)
| Milestone | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Started | 121 |
| Completed | 112 |
| Not completed | 9 |
| Withdrew: Withdrawal by subject | 7 |
| Withdrew: Ineligibility discovered after enrollment | 2 |
| Milestone | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Started | 48 |
| Completed | 31 |
| Not completed | 17 |
| Withdrew: Withdrawal by subject | 13 |
| Withdrew: Recruited during interim analysis | 3 |
| Withdrew: Ineligibility discovered after enrollment | 1 |
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
| correlation coefficient | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A Correlation of Day 29 Estradiol With BMI | 0.06 (-0.13 to 0.24) |
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
| correlation coefficient | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A Correlation of Day 29 Estrone With BMI | 0.07 (-0.12 to 0.25) |
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
| correlation coefficient | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A Correlation of Day 29 Estradiol With Vitamin D | -0.04 (-0.22 to 0.15) |
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
| correlation coefficient | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A Correlation of Day 29 Estrone With Vitamin D | 0.04 (-0.14 to 0.23) |
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
| pmol/L | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part B Change in Estradiol Level After Double Dose of Letrozole | 0.1 (-0.56 to 0.78) |
No measurements were reported for this outcome.
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
| score on a scale | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Day 1 | 62.4 ± 9.6 |
| Day 29 | 62.9 ± 10.4 |
Results for this outcome have not been posted.
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
| score on a scale | Part B |
|---|---|
| Day 29 | 61.7 ± 11.1 |
| Day 58 | 61.2 ± 11.5 |
Collected over Adverse events were collected over the duration of the study: 29 days for patients taking part in Part A only, 58 days for patients that took part in Parts A and B. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Full Study | 0/121 (0%) | 2/121 (1.7%) | 8/121 (6.6%) |
| Event | Full Study |
|---|---|
| Renal Colic/ConstipationRenal and urinary disorders | 1/121 |
| StrokeVascular disorders | 1/121 |
| Event | Full Study |
|---|---|
| ArthralgiaMusculoskeletal and connective tissue disorders | 8/121 |
| Age, Continuous(years) | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A | 61.7 ± 7.6 |
| Part B | 61.0 ± 66 |
| Sex: Female, Male(Participants) | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A — Female | 112 |
| Part A — Male | 0 |
| Part B — Female | 31 |
| Part B — Male | 0 |
| Age at menopause(years) | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A | 49.2 ± 4.7 |
| Part B | 48.4 ± 5.2 |
| Vitamin D supplementation(Participants) | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Part A | 109 |
| Part B | 31 |
| Letrozole use prior to study(months) | Post-menopausal Women Using Adjuvant Letrozole |
|---|---|
| Mean | 18.1 ± 17.6 |
Plan to share: Yes — 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 information: Study protocol, Sap, Icf, Csr
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Samuel Lunenfeld Research Institute, Mount Sinai Hospital