What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving dual anti-HER2 therapy such as trastuzumab and lapatinib, are associated with several side effects. Trastuzumab can cause cardiac toxicity, including heart failure, and infusion-related reactions like fever and chills. Lapatinib often leads to diarrhea, rash, and hepatic adverse events. When combined, these therapies can increase the incidence of these side effects. Simvastatin, which is being studied for its potential to enhance anti-HER2 therapy, is generally well-tolerated but can cause muscle pain, liver enzyme abnormalities, and gastrointestinal issues. Patients undergoing these treatments should be closely monitored for these adverse effects.

What prior FDA approvals exist?

The FDA has approved several anti-HER2 therapies for the treatment of breast cancer. Notable drugs include trastuzumab (Herceptin), which targets the HER2 receptor to inhibit tumor growth, and pertuzumab (Perjeta), which prevents HER2 dimerization. Additionally, ado-trastuzumab emtansine (Kadcyla) combines trastuzumab with a cytotoxic agent to deliver targeted chemotherapy. These therapies are often used in combination to enhance efficacy. The trial involving simvastatin aims to enhance the effectiveness of existing anti-HER2 therapies by potentially inhibiting cell proliferation and inducing apoptosis.

What other types of research exist?

Promising novel alternatives to Simvastatin for enhancing anti-HER2 therapy in breast cancer patients include investigational agents such as regorafenib, cabozantinib, sorafenib, and lenvatinib. These agents have shown limited activity in other cancer types by inhibiting cell proliferation and inducing apoptosis, making them potential candidates for further research in breast cancer treatment.

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Simvastatin + Anti-HER2 Therapy for Breast Cancer (SIMPHONY Trial)

Phase 2

Waitlist Available

Led By Mothaffar Rimawi, MD

Research Sponsored by Baylor Breast Care Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2

Participants must not have undergone major surgery or radiation therapy within 28 days prior to beginning treatment with simvastatin

Must not have

Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medications

Poorly controlled hypertension at the physician's discretion or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA) / stroke within ≤ 6 months prior to the first study treatment, myocardial infarction within ≤ 6 months prior to the first study treatment, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia requiring medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 24 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects from simvastatin may include muscle pain or weakness (rarely leading to serious conditions like rhabdomyolysis), liver problems (indicated by abnormal blood tests), digestive issues such as nausea or constipation, headache, and increased risk of diabetes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I haven't had major surgery or radiation therapy in the last 28 days.

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You must have normal levels of certain blood cells, kidney function, liver function, and heart function. If you have cancer in the brain, it must be stable for at least 3 months. If you can get pregnant, you need to have a negative pregnancy test and agree to use birth control during the study.

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My ER+/HER2+ cancer progressed despite dual anti-HER2 and hormone therapy.

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I am a woman and I am 18 years old or older.

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My breast cancer has spread and cannot be cured with surgery or radiation.

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My ER-/HER2+ cancer did not respond to at least one chemotherapy treatment.

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My cancer is HER2-positive as per specific guidelines.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I do not have serious heart problems or poorly controlled high blood pressure.

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

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I have not taken IV antibiotics for an infection in the last 7 days.

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I have had rhabdomyolysis in the past.

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I have or had HIV, Hepatitis B, or Hepatitis C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response

Secondary study objectives

Clinical benefit

Duration of Response

HMG-CoA Reductase and HMG-CoA Synthase 1 protein levels in baseline and post-treatment tumor biopsies

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: SimvastatinExperimental Treatment1 Intervention

Simvastatin 80 mg in combination with anti-HER2 therapy regimen

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Simvastatin 80mg

2007

Completed Phase 4

~140

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

HER2-targeted therapies, such as trastuzumab and pertuzumab, are designed to bind to the HER2 receptor on breast cancer cells, thereby inhibiting cell proliferation and inducing apoptosis. Simvastatin, a statin, is being studied for its potential to enhance the effectiveness of these therapies by further inhibiting cell proliferation and promoting cancer cell death. This combination could improve treatment outcomes for breast cancer patients by more effectively targeting and eliminating cancer cells.

Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs.