Clinical trial NCT05754528: Evaluating an Endocrine Therapy Dose-frequency Escalation Strategy and Its Effects on Tolerability and Compliance
Official title: A Pragmatic Randomised, Trial Evaluating an Endocrine Therapy Dose-frequency Escalation Strategy and Its Effects on Tolerability and Compliance (REaCT-TEMPO)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Breast Cancer
Keywords: Endocrine Therapy
Endocrine Therapy Toxicity
Dose-frequency escalation
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2023-03-06
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this randomized, pragmatic clinical trial is to evaluate an endocrine therapy dose-frequency escalation strategy and its effects on tolerability and compliance. Participants will be randomized to standard daily dosing of endocrine therapy or endocrine therapy dose-frequency escalation defined as, taking endocrine therapy every other day for 1 month and then daily.

Detailed description: Breast cancer remains the most common cancer diagnosis and second leading cause of cancer death among Canadian women. Close to 70% of breast cancers are hormone-dependent and endocrine therapy is the mainstay treatment (such as tamoxifen, aromatase inhibitors and lutenizing hormone-releasing hormone analogs). Globally, endocrine therapy has led to the greatest benefit for breast cancer patients resulting in compelling reductions in breast cancer recurrence and mortality rates. Tamoxifen and aromatase inhibitors (e.g. letrozole, anastrozole and exemestane) can cause a variable degree of toxicity linked to estrogen deprivation such as: vasomotor symptoms (hot flashes and night sweats), arthralgia/joint stiffness, genitourinary symptoms (vaginal dryness, dysuria, urinary incontinence, recurrent urinary tract infections and pain during sexual intercourse), insomnia, weight gain, mood changes, cognitive dysfunction, fatigue and skin dryness. It is well acknowledged that endocrine therapy side effects can influence treatment adherence, compliance, and persistence. A systematic review of adjuvant endocrine treatment found that 41 to 72% of patients did not take the correct dosage at the prescribed frequency and 31 to 73% discontinued endocrine therapy. Treatment adherence and persistence are key issues in breast cancer, as early cessation or reduced compliance/adherence to hormonal therapy leads to reduced disease-free survival and increased mortality. Despite a plethora of studies aimed at reducing the side effects of endocrine therapy there is no clear evidence that any of them have resulted in improved adherence/compliance/persistence. In practice, it is common to see a clinician reducing dose-intensity or frequency when patients develop intolerable side effects from endocrine therapy, i.e. either using 10 mg instead of 20 mg of Tamoxifen daily, or an every other day schedule for aromatase inhibitors. However, this commonly used practice has not been evaluated in a prospective trial. The researchers propose to conduct the world's first prospective randomized clinical trial to evaluate a dose-frequency escalation strategy of endocrine therapy (meaning taking the dose every other day for 1 month and then daily) and its effects on adherence and tolerability.

Eligibility criteria: Inclusion Criteria:

* Patients with an early stage or locally advanced hormonal receptor positive breast cancer
* Plan to receive endocrine therapy
* Able to provide oral consent
* Willing and able to complete questionnaires as per study protocol

Exclusion Criteria:

* Metastatic cancer
* Adjuvant abemaciclib

Primary outcomes:
measure: 1-year adherence with prescribed endocrine therapy
timeFrame: 1 year after start of endocrine therapy
Secondary outcomes:
measure: Adherence rates with prescribed endocrine therapy
timeFrame: Through study completion, 5 years
measure: Persistence with prescribed endocrine therapy
timeFrame: Through study completion, 5 years
measure: Endocrine toxicity and tolerability
timeFrame: Through study completion, 5 years
measure: Patient health-related quality of life
timeFrame: Through study completion, 5 years
measure: Endocrine therapy interruptions
timeFrame: Through study completion, 5 years
measure: Endocrine therapy discontinuations
timeFrame: Through study completion, 5 years
measure: Endocrine therapy changes
timeFrame: Through study completion, 5 years
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Marie-France Savard, MD
role: PRINCIPAL_INVESTIGATOR
References: