Adjusted Endocrine Therapy for Breast Cancer

(REaCT-TEMPO Trial)

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

240 Participants Needed

Trial Summary

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 evidence supports the effectiveness of endocrine therapy drugs for breast cancer?

Endocrine therapy drugs like tamoxifen and aromatase inhibitors have been shown to improve survival and quality of life in breast cancer patients by reducing the risk of cancer recurrence. Studies indicate that these drugs are effective in both early-stage and metastatic breast cancer, with aromatase inhibitors being particularly beneficial for postmenopausal women. ^{1 2 3 4 5}

What safety data exists for endocrine therapy in breast cancer treatment?

Endocrine therapies like tamoxifen and aromatase inhibitors (anastrozole, letrozole, exemestane) are generally considered safe for treating breast cancer, though they can have side effects. Tamoxifen may increase the risk of endometrial hyperplasia (thickening of the uterus lining) and blood clots, while newer aromatase inhibitors have a more favorable safety profile with fewer serious side effects. ^{5 6 7 8 9}

How is endocrine therapy for breast cancer different from other treatments?

Endocrine therapy for breast cancer is unique because it specifically targets hormone receptor-positive tumors by either reducing estrogen production or blocking its effects, which is different from chemotherapy that targets rapidly dividing cells in general. This therapy includes drugs like tamoxifen and aromatase inhibitors, which are often preferred for their effectiveness and fewer side effects compared to chemotherapy. ^{4 10 11 12 13}

What is the purpose of this trial?

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.

Research Team

Marie-France Savard

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

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

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

I plan to undergo hormone therapy.

I can give my consent verbally.

Exclusion Criteria

I am taking abemaciclib as a follow-up treatment.

My cancer has spread to other parts of my body.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Endocrine therapy for advanced/metastatic breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

Clinical benefit of sequential use of endocrine therapies for metastatic breast cancer. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Endocrine therapy in metastatic breast cancer. [2019]

5. Lebanon pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Role of aromatase inhibitors in the treatment of breast cancer. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Longitudinal trends in utilization of endocrine therapies for breast cancer: an international comparison. [2022]

9. England 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. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Examination of the use of Exemestane in patients with metastatic breast cancer. [2016]

11. Netherlands pubmed.ncbi.nlm.nih.gov

A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women. [2018]

12. Japan pubmed.ncbi.nlm.nih.gov

[CURRENT PERSPECTIVE ON SYSTEMIC THERAPY FOR BREAST CANCER]. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Historical perspective on hormonal therapy of advanced breast cancer. [2022]