Breast Cancer
Conditions
Keywords
Breast Cancer, Endocrine Therapy, Chronotherapy, Chronotherapeutics
Brief summary
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Chronotherapy, also called chronotherapeutics, is defined as the administration of a medication in coordination with circadian rhythm in order to minimize side effects and yield a greater efficacy. The investigators propose to perform a pragmatic, multi-centre, open-label, randomized clinical trial to establish the optimal timing (morning vs. evening) of administering endocrine therapy based on side effects and benefits in early stage breast cancer patients.
Detailed description
Endocrine therapy is an established treatment for hormone receptor-positive breast cancer, but can cause significant side effects with deterioration in quality of life. The side effects of all forms of endocrine therapy are well recognized and can lead to treatment non-persistence or non-compliance. Compliance is defined as the degree or extent of conformity to the recommended administration by the provider, whereas persistence refers to the act of continuing treatment for a certain prescribed duration. Treatment adherence is especially important in breast cancer, as early cessation or reduced compliance to hormonal therapy are associated with reduced disease-free survival and increased mortality. Chronotherapy, also called chronotherapeutics, is defined as the administration of a medication in coordination with circadian rhythm in order to minimize side effects and yield a greater efficacy. The investigators propose to perform a pragmatic, multi-centre, open-label, randomized clinical trial to establish the optimal timing (morning vs. evening) of administering endocrine therapy based on side effects and benefits in early stage breast cancer patients.
Interventions
OTHERMorning administration of endocrine therapy
Endocrine therapy administered within one hour of patient wake up time
OTHEREvening administration of endocrine therapy
Endocrine therapy administered within one hour of the patient bed time
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with an early stage or locally advanced hormonal receptor positive breast cancer * Plan to receive endocrine therapy * 18 years of age or older * Able to provide oral consent * Willing and able to complete questionnaires as per study protocol
Exclusion criteria
* Metastatic cancer * Previous endocrine therapy for breast cancer * Plan to receive adjuvant abemaciclib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endocrine Toxicity and Tolerability at 12 Weeks | Baseline to 12 weeks after treatment initiation | Measured by the change in total Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire from baseline to 12 weeks following the beginning of endocrine therapy. FACT-ES is a validated sub scale of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total range of 0 to 184. Higher FACT-ES scores indicate better outcomes. The current outcome is a change in FACT-ES scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endocrine Toxicity and Tolerability | Baseline, 4, 8, 12 and 52 weeks after treatment initiation | Measured by the change in total score and individual Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaires from baseline to 4, 8, 12 and 52 weeks following the beginning of endocrine therapy. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total score range of 0 to 184. Higher scores indicate better quality of life. The current outcome is a change in FACT-ES scores over time. |
| Change in Health Related Quality of Life Scores | Baseline, 4, 8, 12 and 52 weeks after treatment initiation | Measured by the change in the total score and individual sub scales of the validated Functional Assessment of Cancer Therapy for patients with Breast cancer (FACT-B) questionnaire from baseline to 4, 8, 12 and 52 weeks following the beginning of endocrine therapy. The FACT-B consists of 37 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total score range of 0 to 148. Higher FACT-B scores indicate better quality of life. The current outcome is a change in FACT-B scores over time. |
| Number of Participants Who Were Compliant With ET | 52 weeks after treatment initiation | Rates of non-persistence or non-compliance with initially prescribed endocrine therapy (ET) |
| Cost-effectiveness | 52 weeks after treatment initiation | Incremental cost-effectiveness rations (cost per one quality-adjusted life year (QALY) gained). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rates of Non-compliance to Endocrine Therapy | 52 weeks after treatment initiation | Comparing rates of non-compliance and non-persistence to endocrine therapy with patient age, turmour stage, chemotherapy use and type of endocrine therapy. The rates of non-compliance and rates of non-persistence will be tracked throughout the duration of the study and then compared to patient age, tumour stage, chemotherapy use and the type of endocrine therapy used. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Morning Administration of Endocrine Therapy Administration of endocrine therapy defined as, within one hour of the patient wake up time
Morning administration of endocrine therapy: Endocrine therapy administered within one hour of patient wake up time | 122 |
| Evening Administration of Endocrine Therapy Administration of endocrine therapy defined as, within one hour of the patient bed time
Evening administration of endocrine therapy: Endocrine therapy administered within one hour of the patient bed time | 123 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not want endocrine therapy | 3 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Evening Administration of Endocrine Therapy | Total | Morning Administration of Endocrine Therapy |
|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 11.2 | 61.1 years STANDARD_DEVIATION 11.9 | 61.1 years STANDARD_DEVIATION 12.5 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 123 participants | 245 participants | 122 participants |
| Sex: Female, Male Female | — | 0 Participants | — |
| Sex: Female, Male Male | — | 0 Participants | — |
| Type of endocrine therapy Anastrozole | 22 Participants | 42 Participants | 20 Participants |
| Type of endocrine therapy Exemestane | 0 Participants | 0 Participants | 0 Participants |
| Type of endocrine therapy Letrozole | 7 Participants | 16 Participants | 9 Participants |
| Type of endocrine therapy LHRH | 12 Participants | 22 Participants | 10 Participants |
| Type of endocrine therapy Tamoxifen | 94 Participants | 187 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 122 | 0 / 123 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change in Endocrine Toxicity and Tolerability at 12 Weeks
Measured by the change in total Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire from baseline to 12 weeks following the beginning of endocrine therapy. FACT-ES is a validated sub scale of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total range of 0 to 184. Higher FACT-ES scores indicate better outcomes. The current outcome is a change in FACT-ES scores.
Time frame: Baseline to 12 weeks after treatment initiation
Population: The participants who answered the FACT-ES at baseline and 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Morning Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability at 12 Weeks | -2.2 units on a scale | Standard Deviation 14.1 |
| Evening Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability at 12 Weeks | -5.0 units on a scale | Standard Deviation 16.8 |
Secondary
Change in Endocrine Toxicity and Tolerability
Measured by the change in total score and individual Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaires from baseline to 4, 8, 12 and 52 weeks following the beginning of endocrine therapy. FACT-ES consists of 46 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total score range of 0 to 184. Higher scores indicate better quality of life. The current outcome is a change in FACT-ES scores over time.
Time frame: Baseline, 4, 8, 12 and 52 weeks after treatment initiation
Population: The number analyzed differs from overall number analyzed because not all participants completed the questionnaires at all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morning Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 4 Weeks | -0.3 units on a scale | Standard Deviation 12.6 |
| Morning Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 8 Weeks | -1.6 units on a scale | Standard Deviation 13.7 |
| Morning Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 12 Weeks | -2.2 units on a scale | Standard Deviation 14.1 |
| Morning Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 52 Weeks | -3.0 units on a scale | Standard Deviation 18.7 |
| Evening Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 52 Weeks | -4.7 units on a scale | Standard Deviation 15.6 |
| Evening Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 4 Weeks | -0.5 units on a scale | Standard Deviation 14.6 |
| Evening Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 12 Weeks | -5.0 units on a scale | Standard Deviation 16.8 |
| Evening Administration of Endocrine Therapy | Change in Endocrine Toxicity and Tolerability | Baseline to 8 Weeks | -2.3 units on a scale | Standard Deviation 13.6 |
Secondary
Change in Health Related Quality of Life Scores
Measured by the change in the total score and individual sub scales of the validated Functional Assessment of Cancer Therapy for patients with Breast cancer (FACT-B) questionnaire from baseline to 4, 8, 12 and 52 weeks following the beginning of endocrine therapy. The FACT-B consists of 37 items on a 5 point Likert type scale ranging from 0 (not at all) to 4 (very much), with a total score range of 0 to 148. Higher FACT-B scores indicate better quality of life. The current outcome is a change in FACT-B scores over time.
Time frame: Baseline, 4, 8, 12 and 52 weeks after treatment initiation
Population: The number analyzed differs from the overall number of participants analyzed because not all participants completed all questionnaires at all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Morning Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 12 Weeks | 2.3 units on a scale | Standard Deviation 13.6 |
| Morning Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 8 Weeks | 1.4 units on a scale | Standard Deviation 12.3 |
| Morning Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 52 weeks | 1.9 units on a scale | Standard Deviation 18 |
| Morning Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 4 Weeks | 1.9 units on a scale | Standard Deviation 12 |
| Evening Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 52 weeks | 0.8 units on a scale | Standard Deviation 14.4 |
| Evening Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 8 Weeks | 0.9 units on a scale | Standard Deviation 10.7 |
| Evening Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 12 Weeks | -0.6 units on a scale | Standard Deviation 14.1 |
| Evening Administration of Endocrine Therapy | Change in Health Related Quality of Life Scores | Baseline to 4 Weeks | 1.2 units on a scale | Standard Deviation 11.6 |
Secondary
Cost-effectiveness
Incremental cost-effectiveness rations (cost per one quality-adjusted life year (QALY) gained).
Time frame: 52 weeks after treatment initiation
Secondary
Number of Participants Who Were Compliant With ET
Rates of non-persistence or non-compliance with initially prescribed endocrine therapy (ET)
Time frame: 52 weeks after treatment initiation
Population: This is the modified intention-to-treat population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Morning Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | No interruptions of ET greater than 7 days | 103 Participants |
| Morning Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | Still taking ET | 103 Participants |
| Morning Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | Still taking ET with no interruptions greater than 7 days and no change in ET type | 88 Participants |
| Morning Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | Still taking ET at the assigned time | 105 Participants |
| Evening Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | Still taking ET with no interruptions greater than 7 days and no change in ET type | 84 Participants |
| Evening Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | Still taking ET | 100 Participants |
| Evening Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | No interruptions of ET greater than 7 days | 95 Participants |
| Evening Administration of Endocrine Therapy | Number of Participants Who Were Compliant With ET | Still taking ET at the assigned time | 105 Participants |
Other Pre-specified
Rates of Non-compliance to Endocrine Therapy
Comparing rates of non-compliance and non-persistence to endocrine therapy with patient age, turmour stage, chemotherapy use and type of endocrine therapy. The rates of non-compliance and rates of non-persistence will be tracked throughout the duration of the study and then compared to patient age, tumour stage, chemotherapy use and the type of endocrine therapy used.
Time frame: 52 weeks after treatment initiation
Population: This was an exploratory analysis and it was not performed.