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Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer (SIMPHONY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03324425
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : July 30, 2021
Information provided by (Responsible Party):
Mothaffar Rimawi, Baylor Breast Care Center

Tracking Information
First Submitted Date  ICMJE September 26, 2017
First Posted Date  ICMJE October 27, 2017
Last Update Posted Date July 30, 2021
Actual Study Start Date  ICMJE March 4, 2020
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
Objective Response [ Time Frame: Up to approximately 24 months ]
Objective response is defined as complete response or partial response, according to RECIST criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
  • 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
  • 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
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer
Official Title  ICMJE A Phase II Single Arm Trial of Adding Simvastatin to Dual Anti-HER2 Therapy in Patients With HER2-Positive Metastatic Breast Cancer
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer Stage IV
Intervention  ICMJE Drug: Simvastatin 80mg
Participants will receive simvastatin 80 mg by mouth daily at bedtime
Other Name: Zocor
Study Arms  ICMJE Experimental: Simvastatin
Simvastatin 80 mg in combination with anti-HER2 therapy regimen
Intervention: Drug: Simvastatin 80mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 24, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    1. ANC ≥1.5 x 109/L, platelet count ≥100 x 109/L, haemoglobin ≥ 10 g/dL.
    2. creatinine < 1.5 x UNL (upper normal limit)
    3. Total bilirubin < 1.5x UNL
    4. ALT & AST < 2.5xUNL; alkaline phosphatase < 2.5xUNL;
    5. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anne Pavlick 713-798-7814
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03324425
Other Study ID Numbers  ICMJE H-41818
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Mothaffar Rimawi, Baylor Breast Care Center
Study Sponsor  ICMJE Baylor Breast Care Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Baylor Breast Care Center
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP