Breast Cancer Stage IVPhase 2SIMPHONYNCT03324425
Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer
A Phase 2 study testing Simvastatin 80mg in people with Breast Cancer Stage IV, run by Baylor Breast Care Center at 2 sites in United States.
Trial summary
This study recruits patients with metastatic breast cancer who have progressed on their current regimen of dual anti-HER2 therapy. This study evaluates whether or not the addition of simvastatin to the dual anti-HER2 therapy regimen helps make the tumor respond to the anti-HER2 therapy again. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Stage IV
- What is being tested?
- Simvastatin 80mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Mar 2020to Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent.
- Patients must have histologically confirmed and documented adenocarcinoma of the breast with metastatic disease not amenable to curative therapy.
- Cancer must be HER2-positive, according to ASCO-CAP guidelines. Any ER and PR status is allowed.
- Participants must have documented disease progression while receiving dual anti-HER2 targeted therapy for metastatic breast cancer, as per investigator assessment. Any combination of biologic therapies is acceptable. Prior chemotherapy is acceptable, but patients must have been off cytotoxic chemotherapy for at least 1 month. Patients with ER-/HER2+ disease have must be failed at least 1 line of chemotherapy in the metastatic setting. Patients with ER+/HER2+ disease who progressed on dual anti-HER2 therapy plus endocrine therapy are eligible. Concomitant endocrine therapy is acceptable and may be continued at the discretion of the treating physician.
- Patient must be female and at least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
Show all 19Show fewer
- Patients must have measurable disease, per RECIST criteria v1.1.21
- Participants must not have undergone major surgery or radiation therapy within 28 days prior to beginning treatment with simvastatin. Any toxicity from prior surgical or radiation treatment must have sufficiently resolved prior to study entry, as determined by the treating physician.
- Estimated life expectancy of ≥ 12 weeks.
- Ability to swallow oral medications.
- Participants must have adequate organ function as defined by:
- ANC ≥1.5 x 109/L, platelet count ≥100 x 109/L, haemoglobin ≥ 10 g/dL.
- creatinine < 1.5 x UNL (upper normal limit)
- Total bilirubin < 1.5x UNL
- ALT \& AST < 2.5xUNL; alkaline phosphatase < 2.5xUNL;
- Creatine phosphokinase (CPK) ≤ 2.5 x UNL
- Baseline left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiography (ECHO) or multi gated acquisition (MUGA) scan.
- Patients with CNS metastatic disease are allowed if the disease is controlled and stable for at least 3 months by CT or MRI.
- Negative pregnancy test within 7 days prior to study treatment start, for women of childbearing potential. Women of childbearing potential must agree to use an adequate form of contraception for the duration of their study participation
Who cannot join
- Patients currently treated with a statin or who have been treated with a statin in the past 2 months are ineligible for this study.
- Known hypersensitivity to statins.
- Prior history of rhabdomyolysis.
- Patients who consume more than 3 alcoholic beverages per day.
- 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.
Show all 13Show fewer
- Current severe, uncontrolled systemic disease (e.g. pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures)
- Current or past infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).
- Receipt of IV antibiotics for infection within 7 days of study enrollment.
- History of other malignancies within the last 2 years, except for carcinoma in situ of the cervix or basal cell carcinoma
- Participants with bone-only disease are excluded, unless a measureable lesion is present, as defined by RECIST 1.1.
- Patients who suffer from a medical or psychiatric condition that, in the opinion of the principal investigator, would impair their ability to participate in the study.
- Concurrent interventional studies.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Harris Health System - Smith Clinic
Houston, Texas, 77054
O'Quinn Medical Tower - McNair Campus; Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77054
About this study
Official title: A Phase II Single Arm Trial of Adding Simvastatin to Dual Anti-HER2 Therapy in Patients With HER2-Positive Metastatic Breast Cancer
This study recruits patients with metastatic breast cancer who have progressed on their current regimen of dual anti-HER2 therapy. This study evaluates whether or not the addition of simvastatin to the dual anti-HER2 therapy regimen helps make the tumor respond to the anti-HER2 therapy again. All participants will receive simvastatin in combination with their current anti-HER2 therapy regimen.
Read the detailed description
This study is recruiting participants with metastatic breast cancer that is HER2 positive. "Metastatic" means that cancer has spread to areas of the body outside of the breast. "HER2 positive" means that a cancer cell has too many HER2 receptors on its surface. HER2 receptors act like copy machines, and help tell cancer cells to grow and multiply.
Drugs known as HER2-targeted therapies are often used to treat HER2-positive cancers. HER2-targeted therapies work by blocking the HER2 protein from telling the cell to grow and divide. Once the protein stops working, the cancer cells can no longer make copies of themselves. Once a cancer cell becomes unable to make copies of itself, the tumor will start to shrink. However, some tumors are able to find other ways to make copies of themselves, even when the HER2 protein is blocked. When this happens, the cancer will start to grow again. Researchers believe that adding a drug called simvastatin to an anti-HER2 therapy regimen may cause the cancer to start responding again to your HER2-medications.
Simvastatin is a drug that is approved by the Food and Drug Administration (FDA) to treat high cholesterol. Laboratory research has shown that simvastatin together with dual HER2-targeted therapy slows the growth of breast cancer tumors that had been growing on dual HER2-targeting therapy alone.
- Conditions
- Breast Cancer Stage IV
- Being tested
- Simvastatin 80mg
- Keywords
- breast cancer, metastatic breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 80mgDrug
Also called Zocor
Participants will receive simvastatin 80 mg by mouth daily at bedtime
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin | Experimental | Simvastatin 80 mg in combination with anti-HER2 therapy regimen Receives: Drug: Simvastatin 80mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response
Objective response is defined as complete response or partial response, according to RECIST criteria.
Measured: Up to approximately 24 months
Secondary outcomes (5)
Clinical benefit
Clinical benefit is defined as the number of objective responses plus the number of participants with stable disease lasting greater than 24 weeks
Measured: Up to approximately 24 months
Duration of Response
The length of time participants have a partial response, complete response or stable disease prior to disease progression
Measured: Up to approximately 24 months
Time to Progression
The length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body
Measured: Up to approximately 24 months
Number of treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria v. 4.0 (CTCAE v. 4.0).
This is the number of side effects reported by participants receiving simvastatin in combination with HER2-therapy.
Measured: Up to approximately 24 months
HMG-CoA Reductase and HMG-CoA Synthase 1 protein levels in baseline and post-treatment tumor biopsies
This measures the levels of certain enzymes in a tumor that help scientists understand how simvastatin is affecting the cancer cells.
Measured: Up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start4 Mar 2020
- Primary completionDec 2028 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer Stage IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor Breast Care Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mothaffar Rimawi, Baylor Breast Care Center
- Investigators
- Mothaffar Rimawi, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03324425
- Sponsor's protocol ID
- H-41818
- Acronym
- SIMPHONY
- Status last verified
- Feb 2025
- First submitted
- 26 Sep 2017
- Last updated
- 27 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single Arm Trial of Adding Simvastatin to Dual Anti-HER2 Therapy in Patients With HER2-Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT03324425
- Acronym / sponsor ID
- SIMPHONY / H-41818
- Conditions
- Breast Cancer Stage IV
- Keywords
- breast cancer, metastatic breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Baylor Breast Care CenterUniversity, hospital or other
- Study start
- 4 Mar 2020 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 27 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study recruits patients with metastatic breast cancer who have progressed on their current regimen of dual anti-HER2 therapy. This study evaluates whether or not the addition of simvastatin to the dual anti-HER2 therapy regimen helps make the tumor respond to the anti-HER2 therapy again. All participants will receive simvastatin in combination with their current anti-HER2 therapy regimen.
Detailed description
This study is recruiting participants with metastatic breast cancer that is HER2 positive. "Metastatic" means that cancer has spread to areas of the body outside of the breast. "HER2 positive" means that a cancer cell has too many HER2 receptors on its surface. HER2 receptors act like copy machines, and help tell cancer cells to grow and multiply.
Drugs known as HER2-targeted therapies are often used to treat HER2-positive cancers. HER2-targeted therapies work by blocking the HER2 protein from telling the cell to grow and divide. Once the protein stops working, the cancer cells can no longer make copies of themselves. Once a cancer cell becomes unable to make copies of itself, the tumor will start to shrink. However, some tumors are able to find other ways to make copies of themselves, even when the HER2 protein is blocked. When this happens, the cancer will start to grow again. Researchers believe that adding a drug called simvastatin to an anti-HER2 therapy regimen may cause the cancer to start responding again to your HER2-medications.
Simvastatin is a drug that is approved by the Food and Drug Administration (FDA) to treat high cholesterol. Laboratory research has shown that simvastatin together with dual HER2-targeted therapy slows the growth of breast cancer tumors that had been growing on dual HER2-targeting therapy alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Simvastatin | Experimental | Drug: Simvastatin 80mgSimvastatin 80 mg in combination with anti-HER2 therapy regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed informed consent.
- Patients must have histologically confirmed and documented adenocarcinoma of the breast with metastatic disease not amenable to curative therapy.
- Cancer must be HER2-positive, according to ASCO-CAP guidelines. Any ER and PR status is allowed.
- Participants must have documented disease progression while receiving dual anti-HER2 targeted therapy for metastatic breast cancer, as per investigator assessment. Any combination of biologic therapies is acceptable. Prior chemotherapy is acceptable, but patients must have been off cytotoxic chemotherapy for at least 1 month. Patients with ER-/HER2+ disease have must be failed at least 1 line of chemotherapy in the metastatic setting. Patients with ER+/HER2+ disease who progressed on dual anti-HER2 therapy plus endocrine therapy are eligible. Concomitant endocrine therapy is acceptable and may be continued at the discretion of the treating physician.
- Patient must be female and at least 18 years of age.
Key exclusion criteria (13 listed)
- Patients currently treated with a statin or who have been treated with a statin in the past 2 months are ineligible for this study.
- Known hypersensitivity to statins.
- Prior history of rhabdomyolysis.
- Patients who consume more than 3 alcoholic beverages per day.
- Lack of physical integrity of the upper gastrointestinal tract, clinically significant malabsorption syndrome, or inability to take oral medications.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin 80mgAlso: ZocorParticipants will receive simvastatin 80 mg by mouth daily at bedtime | Drug | Simvastatin |
Primary outcome
Objective Response
Time frame: Up to approximately 24 months
Objective response is defined as complete response or partial response, according to RECIST criteria.
5 secondary outcomes
Clinical benefit
Time frame: Up to approximately 24 months
Duration of Response
Time frame: Up to approximately 24 months
Time to Progression
Time frame: Up to approximately 24 months
Number of treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria v. 4.0 (CTCAE v. 4.0).
Time frame: Up to approximately 24 months
HMG-CoA Reductase and HMG-CoA Synthase 1 protein levels in baseline and post-treatment tumor biopsies
Time frame: Up to approximately 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2025.
- Individual participant dataSharing planned: No
Related trials for Breast Cancer Stage IV
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingObservational study
Improving Survival for Metastatic Lobular Breast Cancer (PLUMB Registry)
Metastatic Breast Cancer, Lobular Breast Carcinoma
RecruitingPhase 1/2
Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mothaffar Rimawi, MD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simvastatin 80mg in people with Breast Cancer Stage IV, run by Baylor Breast Care Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response (time frame: Up to approximately 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.