Aromatase Inhibitor Host Factors Study
Study Details
Study Description
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 |
---|---|---|
N/A |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Other: 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Part A Correlation of Day 29 Estradiol With BMI [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
- Part A Correlation of Day 29 Estrone With BMI [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
- Part A Correlation of Day 29 Estradiol With Vitamin D [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
- Part A Correlation of Day 29 Estrone With Vitamin D [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
- Part B Change in Estradiol Level After Double Dose of Letrozole [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
- Plasma Letrozole [Day 29 and day 58]
- Endocrine Symptoms During Part A of Study [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
- Endocrine Symptoms During Part B of the Study [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
- Musculoskeletal Symptoms [baseline (day 1), day 29 (end of part A) and day 58 (end of part B)]
Eligibility Criteria
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:
-
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 1M9 |
2 | Mount Sinai Hospital | Toronto | Ontario | Canada | M5G 1X5 |
3 | Women's College Hospital | Toronto | Ontario | Canada | M5S 1B1 |
Sponsors and Collaborators
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
Investigators
- Principal Investigator: Srikala Sridhar, M.D., Princess Margaret Hospital, Canada
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AI Host Factors
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI>=25 who completed Part A, on a double dose of letrozole |
Period Title: Part A: All Patients | |
STARTED | 121 |
COMPLETED | 112 |
NOT COMPLETED | 9 |
Period Title: Part A: All Patients | |
STARTED | 48 |
COMPLETED | 31 |
NOT COMPLETED | 17 |
Baseline Characteristics
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI>=25 who completed Part A, on a double dose of letrozole |
Overall Participants | 112 |
Age (years) [Mean (Standard Deviation) ] | |
Part A |
61.7
(7.6)
|
Part B |
61.0
(66)
|
Sex: Female, Male (Count of Participants) | |
Female |
112
100%
|
Male |
0
0%
|
Female |
31
27.7%
|
Male |
0
0%
|
Age at menopause (years) [Mean (Standard Deviation) ] | |
Part A |
49.2
(4.7)
|
Part B |
48.4
(5.2)
|
Vitamin D supplementation (Count of Participants) | |
Part A |
109
97.3%
|
Part B |
31
27.7%
|
Letrozole use prior to study (months) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [months] |
18.1
(17.6)
|
Outcome Measures
Title | Part A Correlation of Day 29 Estradiol With BMI |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Part A |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants 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. |
Measure Participants | 112 |
Number (95% Confidence Interval) [correlation coefficient] |
0.06
|
Title | Part A Correlation of Day 29 Estrone With BMI |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Part A |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants 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. |
Measure Participants | 112 |
Number (95% Confidence Interval) [correlation coefficient] |
0.07
|
Title | Part A Correlation of Day 29 Estradiol With Vitamin D |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Part A |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants 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. |
Measure Participants | 112 |
Number (95% Confidence Interval) [correlation coefficient] |
-0.04
|
Title | Part A Correlation of Day 29 Estrone With Vitamin D |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Part A |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants 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. |
Measure Participants | 112 |
Number (95% Confidence Interval) [correlation coefficient] |
0.04
|
Title | Part B Change in Estradiol Level After Double Dose of Letrozole |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Part B participants |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants 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. |
Measure Participants | 31 |
Mean (95% Confidence Interval) [pmol/L] |
0.1
|
Title | Plasma Letrozole |
---|---|
Description | |
Time Frame | Day 29 and day 58 |
Outcome Measure Data
Analysis Population Description |
---|
Data were not collected |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part B Double Dose Letrozole in overweight/obese participants 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. |
Measure Participants | 0 |
Title | Endocrine Symptoms During Part A of Study |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Post-menopausal Women Using Adjuvant Letrozole |
---|---|
Arm/Group Description | Part A: All patients enrolled, on standard of care letrozole |
Measure Participants | 112 |
Day 1 |
62.4
(9.6)
|
Day 29 |
62.9
(10.4)
|
Title | Musculoskeletal Symptoms |
---|---|
Description | |
Time Frame | baseline (day 1), day 29 (end of part A) and day 58 (end of part B) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Endocrine Symptoms During Part B of the Study |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Part B |
---|---|
Arm/Group Description | Part B: Patients With BMI>=25, on double dose of letrozole |
Measure Participants | 31 |
Day 29 |
61.7
(11.1)
|
Day 58 |
61.2
(11.5)
|
Adverse Events
Time Frame | 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 | |
---|---|---|
Adverse Event Reporting Description | National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.01 | |
Arm/Group Title | Full Study | |
Arm/Group Description | Adverse events collected during part A, 29 days of monitored adherence to standard of care letrozole and Part B . | |
All Cause Mortality |
||
Full Study | ||
Affected / at Risk (%) | # Events | |
Total | 0/121 (0%) | |
Serious Adverse Events |
||
Full Study | ||
Affected / at Risk (%) | # Events | |
Total | 2/121 (1.7%) | |
Renal and urinary disorders | ||
Renal Colic/Constipation | 1/121 (0.8%) | 1 |
Vascular disorders | ||
Stroke | 1/121 (0.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Full Study | ||
Affected / at Risk (%) | # Events | |
Total | 8/121 (6.6%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 8/121 (6.6%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. David Cescon |
---|---|
Organization | Princess Margaret Hospital |
Phone | 416-946-2000 |
dave.cescon@uhn.on.ca |
- AI Host Factors