Overview

Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer

Status:
Recruiting
Trial end date:
2025-12-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Baylor Breast Care Center
Treatments:
Simvastatin
Trastuzumab
Criteria
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.