Medication Switch for Breast Cancer

(SWIVEL Trial)

Overseen By Kristina M. Willey

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dartmouth-Hitchcock Medical Center

Must be taking: Aromatase inhibitors

Must not be taking: Tamoxifen

Disqualifiers: Pregnancy, Lactation, Prisoners, others

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

Compensation: Varies

Number of Visits: 8

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to prevent breast cancer from returning by making it easier for women to adhere to aromatase inhibitor (AI) therapy, which lowers estrogen levels to reduce cancer risk. Many women find it challenging to complete the standard 5-year AI treatment due to side effects. Participants will either switch to a different AI or receive proven treatments to manage these side effects. Women who have undergone breast cancer surgery, have estrogen receptor-positive cancer, and are post-menopausal are suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it does require that you have not had any endocrine therapy for cancer in the last 10 years. You should discuss your current medications with the trial team to see if they are compatible with the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that aromatase inhibitors, such as Letrozole, effectively treat hormone-responsive breast cancer. However, many women discontinue their use due to side effects like joint pain and hot flashes. Studies suggest that switching to a different aromatase inhibitor might alleviate these symptoms.

Regarding safety, aromatase inhibitors have been linked to positive outcomes, including a reduced risk of dying from breast cancer. However, they can also increase the risk of heart disease. The current trial explores different strategies to manage these side effects, aiming to help women continue their treatment more comfortably. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a new approach to managing side effects in breast cancer treatment. Unlike typical treatments that often continue with the same aromatase inhibitor despite side effects, this study investigates switching to a different aromatase inhibitor to see if it improves patients' quality of life. Additionally, the trial examines the effectiveness of guideline-directed interventions, which may include non-medication options, offering a comprehensive strategy to manage side effects. This approach could lead to more personalized and effective treatment plans for breast cancer patients experiencing adverse effects.

What evidence suggests that this trial's treatments could be effective for preventing breast cancer recurrence?

Studies have shown that aromatase inhibitors (AIs) effectively reduce the risk of breast cancer returning after surgery. Women who complete five years of AI treatment have a lower chance of dying from breast cancer compared to those who take tamoxifen. However, many women stop taking AIs due to side effects. In this trial, participants reporting side effects from Letrozole will either switch to a different AI or receive guideline-directed interventions (GDI) to manage side effects. Research suggests that switching to a different AI can lessen these side effects, making it easier for women to continue treatment. This approach aims to improve adherence by making the treatment more manageable, potentially increasing its overall effectiveness in preventing breast cancer recurrence. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for women who have undergone surgery for breast cancer and are prescribed aromatase inhibitors to prevent recurrence. They must be experiencing side effects from the treatment but haven't yet completed the standard 5-year therapy.

Inclusion Criteria

I am a woman over 18, post-menopausal for more than 2 years or over 1 year with specific hormone levels.

Ability to give informed consent

Patients must meet the following clinical laboratory criteria: Absolute neutrophil count (ANC) >1,000/mm3 and platelet count > 75,000/mm3, Total bilirubin <1.5 x the upper limit of the normal range (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x ULN

Exclusion Criteria

Prisoners

I haven't had breast cancer treatment, except for bone issues.

I am taking tamoxifen as my first hormone therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline symptom burden and quality of life assessed by validated surveys prior to starting AI

1 week

1 visit (in-person)

Treatment

Participants receive aromatase inhibitor therapy and are monitored for side effects, with randomization to 'switch' or GDI if side effects are significant

6 months

Bi-weekly contact initially, then monthly (virtual/in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with urine samples collected for adherence assessment

24 months

Routine office visits for urine collection at 6, 12, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Switch

Trial Overview The study compares two approaches: a 'Switch' strategy, where patients change their medication, versus Guideline Directed Intervention (GDI), which involves managing side effects without changing drugs. The goal is to help women continue their treatment.

How Is the Trial Designed?

Group I: Switch Active Control 1 Intervention

Participants (people taking part in this study) enrolled to this study will receive treatment with the aromatase inhibitor (AI) Letrozole and fill out surveys to check for side effects to see how the side effects are making their daily life harder. If side effects are reported, the Participant will be randomized (placed by chance) to a group where they will receive either a different AI ('switch') or receive guideline directed intervention "GDI" using medication and non-medication treatment options.

Group II: Guideline Directed Intervention (GDI) Active Control 1 Intervention

Participants will receive evidence-based (proven to work) treatment options for side effects according to national guidelines; these may include medications or non-medication options (guideline-directed interventions, GDIs).

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3341106/

Predictors of Aromatase Inhibitor Discontinuation as a ... Aromatase inhibitors (AIs) are effective for treatment of hormone receptor–positive breast cancer, but adherence and persistence with therapy are poor.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589537025000483

Adjuvant endocrine treatment strategies for non-metastatic ... Following five years of tamoxifen, continuation with five additional years of AI was associated with improved 8-year DFS (85.8%) compared to no extended therapy ...

3. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(15)61074-1/fulltext

Aromatase inhibitors versus tamoxifen in early breast cancer 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e13098

Switching from nonsteroidal aromatase inhibitors to ... HR+ breast cancer patients exhibited a significant decrease in all menopausal symptoms when switching from nonsteroidal to steroidal AI.

5. esmoopen.com esmoopen.com/article/S2059-7029(24)01874-X/fulltext

Comparative overall survival of CDK4/6 inhibitors plus an ... Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305737209001923

Adjuvant aromatase inhibitor therapy: Outcomes and safety The third-generation AIs have shown a significant disease-free survival (DFS) benefit over TAM in the treatment of hormone-responsive early breast cancer (EBC) ...

7. academic.oup.com academic.oup.com/jncics/article/9/1/pkaf009/7985584

Duration of aromatase inhibitor use and long-term ... The associations of the duration of AI use with CVD and mortality outcomes using six years after breast cancer diagnosis as the landmark.

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ... These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...