Adjusted Endocrine Therapy for Breast Cancer

(REaCT-TEMPO Trial)

Not currently recruiting at 1 trial location

Overseen By Deanna Saunders

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must be taking: Endocrine therapy

Must not be taking: Abemaciclib

Disqualifiers: Metastatic cancer

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how different dosing schedules of endocrine therapy affect individuals with breast cancer. It compares taking the medication daily to starting every other day for a month before switching to daily. The main goal is to determine which method is easier to manage and adhere to. Individuals with early-stage or locally advanced hormone receptor-positive breast cancer who plan to start endocrine therapy might be suitable candidates. As a Phase 4 trial, this research aims to understand how the already FDA-approved treatment benefits a broader range of patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking adjuvant abemaciclib, you cannot participate in this trial.

What is the safety track record for endocrine therapy?

Research has shown that endocrine therapy is usually well-tolerated and effective in treating breast cancer. For example, studies have found that taking tamoxifen, a common type of endocrine therapy, for five years can lower the chance of cancer returning by 40% and reduce the risk of death by 30%. This suggests the treatment is both effective and safe for long-term use.

Other studies indicate that aromatase inhibitors, another type of endocrine therapy, can lead to a 53% decrease in breast cancer cases among participants. These findings highlight the potential benefits and safety of the treatment.

Overall, research supports endocrine therapy as a safe option for many patients. While some side effects can occur, these studies suggest that the benefits often outweigh the risks for those receiving treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the adjusted endocrine therapy for breast cancer because it explores a new dosing approach that could enhance patient outcomes. Unlike the standard daily dosing, this method gradually escalates the frequency of the medication, starting with every other day and moving to daily intake. This innovative schedule might reduce side effects and improve adherence, offering a more personalized treatment experience for patients. By adjusting how often the therapy is administered, researchers hope to strike a better balance between effectiveness and tolerability, making treatment more manageable for patients.

What is the effectiveness track record for endocrine therapy in treating breast cancer?

Research shows that endocrine therapy effectively treats breast cancer by blocking hormones that promote cancer cell growth. This trial will compare different dosing strategies of endocrine therapy. One arm involves dose-frequency escalation, where participants take endocrine therapy every other day for 1 month and then daily. The other arm follows the standard daily dosing of endocrine therapy. Studies have found that anastrozole, a type of endocrine therapy, works better than tamoxifen for postmenopausal women with breast cancer. Another study discovered that different dosing schedules of exemestane, another endocrine therapy, can effectively manage cancers driven by estrogen. Overall, endocrine therapy is a proven treatment for breast cancer, with evidence supporting its use in various dosing strategies. ^{6 7 8 9 10}

Who Is on the Research Team?

Marie-France Savard

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for patients with early stage or locally advanced hormone receptor-positive breast cancer who plan to receive endocrine therapy. They must be able to give oral consent and complete study questionnaires. Patients with metastatic cancer or those receiving adjuvant abemaciclib are excluded.

Inclusion Criteria

I can give my consent verbally.

Willing and able to complete questionnaires as per study protocol

My breast cancer is in an early stage and is hormone receptor positive.

Exclusion Criteria

My cancer has spread to other parts of my body.

I am taking abemaciclib as a follow-up treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either standard daily dosing or dose-frequency escalation of endocrine therapy

1 year

Monthly visits (in-person or virtual)

Follow-up

Participants are monitored for safety, adherence, and quality of life after treatment

5 years

Annual visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Endocrine therapy

Trial Overview

The study compares two ways of taking endocrine therapy: the usual daily dose versus starting every other day for a month, then daily. The aim is to see which method has better tolerability and adherence in participants.

How Is the Trial Designed?

Group I: Endocrine therapy dose-frequency escalation Experimental Treatment 1 Intervention

Endocrine therapy dose-frequency escalation defined as, taking endocrine therapy every other day for 1 month and then daily.

Group II: Standard daily dosing of endocrine therapy Active Control 1 Intervention

Standard daily dosing of endocrine therapy

Endocrine therapy is already approved in United States, European Union for the following indications:

Approved in United States as Tamoxifen for:

• Adjuvant treatment of ER-positive early-stage breast cancer
• Treatment of metastatic breast cancer
• Risk reduction of breast cancer in high-risk women

Approved in United States as Anastrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Letrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Exemestane for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Fulvestrant for:

• Treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer
• Treatment of postmenopausal women with HR-positive advanced breast cancer with disease progression on endocrine therapy

Approved in United States as Elacestrant for:

• Treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Approved in European Union as Tamoxifen for:

• Adjuvant treatment of ER-positive early-stage breast cancer
• Treatment of metastatic breast cancer
• Risk reduction of breast cancer in high-risk women

Approved in European Union as Anastrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Letrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Exemestane for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Fulvestrant for:

• Treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer
• Treatment of postmenopausal women with HR-positive advanced breast cancer with disease progression on endocrine therapy

Approved in European Union as Elacestrant for:

• Treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Published Research Related to This Trial

In a study of 81 patients with metastatic breast cancer, Exemestane (EXE) demonstrated moderate efficacy as a second-line treatment, achieving a clinical benefit rate (CBR) of 39% after Anastrozole (ANA) failed.

Patients with only bone and soft tissue metastases had better outcomes with EXE compared to those with visceral metastases, suggesting that EXE may be particularly effective in certain metastatic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of the use of Exemestane in patients with metastatic breast cancer. Takashima, S., Kiyoto, S., Takahashi, M., et al.[2016]

Tamoxifen is the standard treatment for postmenopausal women with hormone-sensitive early breast cancer, but it has side effects that have led researchers to look for safer alternatives.

Third-generation aromatase inhibitors like anastrozole, letrozole, and exemestane have shown better efficacy and a more favorable side effect profile compared to tamoxifen in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. Grana, G.[2018]

In a study of 3887 post-menopausal patients with hormone receptor-positive early breast cancer, over 85% persisted with letrozole treatment for 12 months, but 14.6% discontinued, primarily due to side effects.

Musculoskeletal symptoms and sleep disorders were the most significant adverse events leading to treatment discontinuation, with hazard ratios of 2.55 and 1.95, respectively, indicating a strong need for targeted compliance programs to support patients experiencing these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. Nabieva, N., Fehm, T., Häberle, L., et al.[2022]

Endocrine therapy is a key treatment for metastatic breast cancer, offering effective and minimally toxic options, with tamoxifen being the preferred first-line therapy for both premenopausal and postmenopausal women.

Research is ongoing to develop new 'pure' antiestrogens and to combine endocrine therapy with biologic agents, which may enhance treatment effectiveness in both early and advanced stages of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy in metastatic breast cancer. Kimmick, GG., Muss, HB.[2019]

Fulvestrant is a selective estrogen receptor down-regulator (SERD) that has shown significant efficacy and a strong safety profile in treating postmenopausal women with hormone-receptor positive metastatic breast cancer.

Combining fulvestrant with targeted therapies has demonstrated increased effectiveness, suggesting it may become a new standard treatment, with ongoing clinical trials (FALCON and FEVEX) expected to provide further insights into its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. Poggio, F., Lambertini, M., Blondeaux, E., et al.[2018]

Tamoxifen, while a long-standing treatment for early breast cancer, only prevents about half of relapses and can lead to serious side effects like endometrial hyperplasia and venous thromboembolism due to its estrogenic activity.

Aromatase inhibitors are emerging as a more effective alternative, showing benefits in various treatment settings, including extending therapy after tamoxifen and providing upfront adjuvant therapy, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. Chahine, G., Howayek, M., Atallah, D.[2013]

A longitudinal study from 2001 to 2012 across nine developed countries showed a significant shift in breast cancer treatment from tamoxifen to aromatase inhibitors, with aromatase inhibitors making up over half of total endocrine therapy use by 2012.

The study found that while tamoxifen use stabilized or slightly increased, the overall trend towards aromatase inhibitors aligns with clinical guidelines recommending their use for post-menopausal women, indicating a change in treatment practices based on evolving evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal trends in utilization of endocrine therapies for breast cancer: an international comparison. Kelly, E., Lu, CY., Albertini, S., et al.[2022]

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