Simvastatin + Anti-HER2 Therapy for Breast Cancer

(SIMPHONY Trial)

Not currently recruiting at 3 trial locations

Overseen By Kristen Otte

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Baylor Breast Care Center

Must be taking: Anti-HER2 therapy

Must not be taking: Statins

Disqualifiers: HIV, Hepatitis B/C, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding simvastatin (also known as Zocor) to current anti-HER2 therapy can improve tumor response in people with HER2-positive metastatic breast cancer. It targets patients whose cancer has progressed despite dual anti-HER2 therapy. Participants must have incurable metastatic breast cancer, be experiencing disease progression, and not have undergone major surgery or radiation in the past 28 days. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you will continue your current anti-HER2 therapy while adding simvastatin. If you are on a statin, you cannot participate in the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that simvastatin, a drug commonly used to lower cholesterol, is being tested for safety and effectiveness when combined with anti-HER2 therapy for breast cancer. The FDA has already approved simvastatin for treating high cholesterol, indicating it is generally well-tolerated.

In studies with patients using similar treatments, simvastatin showed promise without major safety concerns. Specifically, research found that patients taking statins, like simvastatin, did not experience significant side effects when used with cancer therapies. This suggests that adding simvastatin to an anti-HER2 treatment might be safe for most patients.

While any treatment can have risks, previous findings and its approved use for cholesterol suggest that simvastatin could be a safe option for patients in this trial. Patients should always consult their healthcare provider for personal medical advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Simvastatin combined with anti-HER2 therapy is unique because it introduces a cholesterol-lowering drug, typically used for heart conditions, into the fight against breast cancer. Researchers are excited about this approach because simvastatin may enhance the effectiveness of existing HER2-targeted therapies by potentially disrupting cancer cell metabolism and growth. Unlike standard treatments that primarily focus on blocking HER2 receptors, this combination aims to exploit a different pathway, offering a promising new angle in the battle against HER2-positive breast cancer.

What evidence suggests that simvastatin might be an effective treatment for metastatic breast cancer?

This trial will evaluate the combination of simvastatin with anti-HER2 therapy for breast cancer. Research has shown that adding simvastatin to anti-HER2 therapy might restore the effectiveness of breast cancer treatments. In earlier studies, simvastatin combined with other cancer treatments resulted in more tumors shrinking or halting their growth. Some research also found that patients taking statins, like simvastatin, with HER2-targeting drugs experienced longer periods without cancer recurrence. These findings suggest that simvastatin could enhance the effectiveness of current treatments for patients whose cancer no longer responds to dual anti-HER2 therapy. While more research is needed, these early results are promising for improving treatment outcomes. ^{3 4 5 6 7}

Who Is on the Research Team?

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with metastatic breast cancer that's HER2-positive and has progressed despite anti-HER2 therapy. They must have measurable disease, adequate organ function, controlled CNS metastases if present, and a life expectancy of at least 12 weeks. Exclusions include recent statin use, hypersensitivity to statins, severe diseases, certain infections like HIV/HBV/HCV, other recent cancers except some skin cancers or cervical carcinoma in situ.

Inclusion Criteria

I am on hormone therapy for my condition, and my doctor can decide if it continues.

I can take care of myself but might not be able to do heavy physical work.

I have not had chemotherapy in the last month.

Exclusion Criteria

You drink more than three alcoholic drinks every day.

I cannot take pills due to issues with my stomach or intestines.

I do not have any severe, uncontrolled diseases right now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive simvastatin in combination with their current anti-HER2 therapy regimen

Up to approximately 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Simvastatin

Trial Overview The study tests the effectiveness of adding simvastatin (80mg) to existing dual anti-HER2 therapy in patients whose tumors no longer respond to this treatment. All participants will continue their current anti-HER2 regimen plus the added simvastatin.

How Is the Trial Designed?

Group I: Simvastatin Experimental Treatment 1 Intervention

Simvastatin 80 mg in combination with anti-HER2 therapy regimen

Who Is Running the Clinical Trial?

Baylor Breast Care Center

Lead Sponsor

Trials

16

Recruited

750+

Published Research Related to This Trial

Targeted agents like CDK4/6 inhibitors have improved outcomes for patients with HR-positive, HER2-negative metastatic breast cancer compared to traditional endocrine therapies, but they come with complex and potentially severe adverse events that require careful management.

Despite the increased risk of hematologic toxicities and the need for more frequent physician visits, these side effects are generally manageable without needing to consult specialists, highlighting the importance of a multidisciplinary approach in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success. Cazzaniga, ME., Danesi, R., Girmenia, C., et al.[2020]

In a study of 225 breast cancer patients, it was found that all participants had at least one actionable pharmacogenetic variant that could inform better prescribing decisions for their medications, potentially improving treatment outcomes.

The research highlights the importance of pre-emptive pharmacogenetic testing, as it could help tailor drug and dose selection to enhance efficacy and reduce adverse events associated with polypharmacy in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer. Bernard, PS., Wooderchak-Donahue, W., Wei, M., et al.[2021]

The SystHERs study is a large, prospective observational cohort study designed to enroll approximately 1000 patients with HER2-positive metastatic breast cancer over 3 years, aiming to gather real-world data on treatment patterns and long-term outcomes.

This study will provide valuable insights into the efficacy and safety of HER2-targeted therapies, as well as patient-reported outcomes, with a follow-up period of up to 8 years, enhancing our understanding of this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SystHERs registry: an observational cohort study of treatment patterns and outcomes in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Tripathy, D., Rugo, HS., Kaufman, PA., et al.[2021]

Targeted therapies, including CDK4/6 inhibitors and PI3K/AKT/mTOR pathway inhibitors, show promising clinical activity and acceptable toxicity in treating hormone receptor-positive, HER2-negative advanced breast cancer, offering new options beyond traditional endocrine therapy.

Immunotherapies targeting PD1/PD-L1 and CTLA-4 have demonstrated potential antitumor responses, indicating a new avenue for treatment in this breast cancer subtype, which is currently being explored in clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). Song, Y., He, L., Wang, Y., et al.[2021]

Aromatase inhibitors (AIs) are more effective than tamoxifen for treating estrogen receptor-positive (ER+)/HER2+ breast cancer, particularly in the adjuvant setting.

Combining HER2-targeted therapy, like trastuzumab, with AIs significantly improves progression-free survival and response rates in postmenopausal women, suggesting a beneficial interaction between HER2 and estrogen receptor signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of biologic therapy and chemotherapy in hormone receptor- and HER2-positive breast cancer. Buzdar, AU.[2020]

Citations

1. withpower.com withpower.com/trial/simvastatin-anti-her2-therapy-for-breast-cancer-e172e

Simvastatin + Anti-HER2 Therapy for Breast Cancer Trial Overview The study tests the effectiveness of adding simvastatin (80mg) to existing dual anti-HER2 therapy in patients whose tumors no longer respond to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8524017/

Combination of Simvastatin and FAC Improves Response to ... This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0925443924004514

Additional statin treatment enhances the efficacy of HER2 ... Consistently, retrospective analysis showed a longer recurrence-free survival in Rac1-high/HER2-positive BC patients treated with HER2-targeting agents with ...

4. link.springer.com link.springer.com/article/10.1007/s10549-025-07699-2

Association of statin use on survival outcomes of patients ... We explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-01063

Addition of Simvastatin to Dual Anti-HER2 Therapy for the ... This phase II trial studies the effect of adding simvastatin to dual anti-HER2 therapy in treating patients with HER2-positive breast cancer that has spread ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03324425

Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic ... This study recruits patients with metastatic breast cancer who have progressed on their current regimen of dual anti-HER2 therapy.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12086115/

Association of statin use on survival outcomes of patients with ... We explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial.