Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer

NCT03324425 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: H-41818
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer Stage IV

Keywords

breast cancer; metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response

  Objective response is defined as complete response or partial response, according to RECIST criteria.

  Up to approximately 24 months

Secondary Outcomes (5)

• Clinical benefit

  Up to approximately 24 months

• Duration of Response

  Up to approximately 24 months

• Time to Progression

  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).

  Up to approximately 24 months

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

  Up to approximately 24 months

Study Arms (1)

Simvastatin

EXPERIMENTAL

Simvastatin 80 mg in combination with anti-HER2 therapy regimen

Drug: Simvastatin 80mg

Interventions

Simvastatin 80mg DRUG

Participants will receive simvastatin 80 mg by mouth daily at bedtime

Also known as: Zocor

Simvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor Breast Care Center: lead

Study Sites (2)

Harris Health System - Smith Clinic

Houston, Texas, 77054, United States

Location

O'Quinn Medical Tower - McNair Campus; Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77054, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Mothaffar Rimawi, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: October 27, 2017
• Study Start: March 4, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)