Simvastatin + Anti-HER2 Therapy for Breast Cancer

(SIMPHONY Trial)

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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if adding simvastatin, a cholesterol-lowering drug, to the current treatment can help patients with advanced breast cancer that has spread and is not responding to usual treatments. The goal is to see if this combination can make the cancer treatment work better. Simvastatin, originally used to lower cholesterol, has been studied since the 1990s for its potential anticancer effects, including in breast cancer.

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.

What data supports the effectiveness of the drug Simvastatin + Anti-HER2 Therapy for breast cancer?

The research highlights that HER2-targeted therapies have significantly changed the course of HER2-positive breast cancer, suggesting that combining these therapies with other agents, like Simvastatin, could potentially improve outcomes. Although specific data on Simvastatin in this combination is not provided, the general success of HER2-targeted treatments offers a promising context for exploring new combinations. ^{1 2 3 4 5}

Is Simvastatin safe for use in humans?

Simvastatin, also known as Zocor, is generally considered safe for use in humans, but like many medications, it can have side effects. It's important to monitor for any adverse effects, especially if used in combination with other drugs, as interactions can occur. ^{6 7 8 9 10}

How is the Simvastatin + Anti-HER2 Therapy different from other breast cancer treatments?

This treatment combines simvastatin, a drug typically used to lower cholesterol, with anti-HER2 therapy, which targets a specific protein that can promote the growth of cancer cells. This combination is unique because it explores the potential of simvastatin to enhance the effectiveness of existing HER2-targeted therapies, offering a novel approach for patients who may not respond well to standard treatments. ^{2 6 11 12 13}

Research Team

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2021]

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

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Primary predictors of survival outcomes for HER2-positive advanced breast cancer patients initiating ado-trastuzumab emtansine. [2020]

4. England pubmed.ncbi.nlm.nih.gov

What therapies are on the horizon for HER2 positive breast cancer? [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race. [2023]

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

Statin use in patients with hormone receptor-positive metastatic breast cancer treated with everolimus and exemestane. [2023]

7. Greece 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). [2021]

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

Cardiovascular Toxicity and Management of Targeted Cancer Therapy. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer. [2021]

10. Netherlands 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. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting HER2 Positive Breast Cancer with Chemopreventive Agents. [2020]

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

Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host. [2021]

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

Clinical Challenges in the Management of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review. [2021]