- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03324425
Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer (SIMPHONY)
A Phase II Single Arm Trial of Adding Simvastatin to Dual Anti-HER2 Therapy in Patients With HER2-Positive Metastatic Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Kristen Otte
- Phone Number: 713-798-8874
- Email: otte@bcm.edu
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77054
- Harris Health System - Smith Clinic
-
Houston, Texas, United States, 77054
- O'Quinn Medical Tower - McNair Campus; Dan L Duncan Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Simvastatin
Simvastatin 80 mg in combination with anti-HER2 therapy regimen
|
Participants will receive simvastatin 80 mg by mouth daily at bedtime
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response
Time Frame: Up to approximately 24 months
|
Objective response is defined as complete response or partial response, according to RECIST criteria.
|
Up to approximately 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical benefit
Time Frame: Up to approximately 24 months
|
Clinical benefit is defined as the number of objective responses plus the number of participants with stable disease lasting greater than 24 weeks
|
Up to approximately 24 months
|
Duration of Response
Time Frame: Up to approximately 24 months
|
The length of time participants have a partial response, complete response or stable disease prior to disease progression
|
Up to approximately 24 months
|
Time to Progression
Time Frame: Up to approximately 24 months
|
The length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body
|
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
|
This is the number of side effects reported by participants receiving simvastatin in combination with HER2-therapy.
|
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
|
This measures the levels of certain enzymes in a tumor that help scientists understand how simvastatin is affecting the cancer cells.
|
Up to approximately 24 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mothaffar Rimawi, MD, Baylor College of Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-41818
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer Stage IV
-
University of Colorado, DenverActive, not recruitingStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Albert Einstein College of MedicineNational Cancer Institute (NCI)Active, not recruitingStage IV Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of California, San FranciscoMerck Sharp & Dohme LLCTerminatedAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8United States
-
Wake Forest University Health SciencesCompletedStage I Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
NSABP Foundation IncCompletedBreast Cancer | Stage IV Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIB Breast Cancer | Locally AdvancedUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-positive Breast CancerUnited States
-
Eske Corporation S.A.CTerminatedBreast Cancer Stage IV | Breast Cancer Stage IIIA | Breast Cancer, Stage IIIBPeru
-
Indiana University School of MedicineBreast Cancer Research FoundationCompletedQuantitation of Endothelial Progenitor Cells as Markers of Tumor Angiogenesis in Breast Cancer (EPC)Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage IIUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Roswell Park Cancer InstituteRecruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Metastatic Breast CarcinomaUnited States
Clinical Trials on Simvastatin 80mg
-
University of Sao PauloCompletedCoronary Heart Disease
-
Helsinki University Central HospitalUniversity of Helsinki; Academy of FinlandCompletedLiver Failure | Heart Failure | Respiratory Failure | Kidney Failure | TransplantationFinland
-
Brasilia Heart Study GroupCompletedMyocardial InfarctionBrazil
-
Johns Hopkins UniversityMerck Sharp & Dohme LLC; Surgi-Vision IncCompletedHeart DiseasesUnited States
-
Cambridge University Hospitals NHS Foundation TrustUniversity of CambridgeActive, not recruitingCardiovascular Diseases | AtherosclerosisUnited Kingdom
-
GenfitCompletedType II Diabetes MellitusBosnia and Herzegovina, Latvia, Macedonia, The Former Yugoslav Republic of, Moldova, Republic of, Romania, Serbia
-
Nanjing Zenshine PharmaceuticalsNot yet recruiting
-
GenfitCompletedImpaired Glucose Tolerance | Abdominal ObesityFrance
-
GenfitCompletedAbdominal Obesity | Atherogenic DyslipidaemiaFrance, Romania, Tunisia
-
Bright Future Pharmaceuticals Factory O/B Bright...Chinese University of Hong KongCompleted