Breast NeoplasmsNCT01669343
Aromatase Inhibitor Host Factors Study
A study testing Letrozole in people with Breast Neoplasms, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 3 sites in Canada.
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… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 3 sitesCanada
- Study dates
- Oct 2012to Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Princess Margaret Hospital
Toronto, Ontario, M5G 1M9
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Women's College Hospital
Toronto, Ontario, M5S 1B1
About this study
Official title: Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole
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.
Read the 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.
- Conditions
- Breast Neoplasms
- Being tested
- Letrozole
- Keywords
- Aromatase Inhibitors
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Also called Femara
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.
| Study group | Role | What they receive |
|---|---|---|
| Post-menopausal Women Using Adjuvant Letrozole | Other | Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 29 to Day 58
Secondary outcomes (3)
Plasma Letrozole
Measured: 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
Measured: 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
Measured: day 29 (end of part A) and day 58 (end of part B)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2012 (estimated)
- Study startOct 2012
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Srikala Sridhar, M.D., Principal investigator, Princess Margaret Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01669343
- Sponsor's protocol ID
- AI Host Factors
- Status last verified
- May 2017
- First submitted
- 15 Aug 2012
- Last updated
- 13 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- 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
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole
- ClinicalTrials.gov ID
- NCT01669343
- Acronym / sponsor ID
- AI Host Factors
- Conditions
- Breast Neoplasms
- Keywords
- Aromatase Inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Samuel Lunenfeld Research Institute, Mount Sinai HospitalUniversity, hospital or other
- Study start
- Oct 2012 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 21 Aug 2012 (estimated)
- Results
- Posted 13 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Post-menopausal Women Using Adjuvant Letrozole | Other | Drug: LetrozolePart A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- Known abnormal liver or renal function defined by:
- Presence of persistent local or known metastatic cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozoleAlso: FemaraPart 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. | Drug | Post-menopausal Women Using Adjuvant Letrozole |
Primary outcome
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
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
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
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
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
3 secondary outcomes
Plasma Letrozole
Time frame: Day 29 and day 58
Endocrine Symptoms During Part A of Study
Time frame: baseline, day 29 (end of part A)
Endocrine Symptoms During Part B of the Study
Time frame: day 29 (end of part A) and day 58 (end of part B)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srikala Sridhar, M.D. principal investigator
Princess Margaret Hospital, Canada
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Letrozole in people with Breast Neoplasms, run by Samuel Lunenfeld Research Institute, Mount Sinai Hospital at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A Correlation of Day 29 Estradiol With BMI (time frame: Day 29). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2021.