NCT02096588

Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin

Terminated Phase 2 Results posted Last updated 9 July 2024

What this trial tests

Phase 2 trial testing Simvastatin in Breast Cancer in 34 participants. Terminated before completion.

Timeline

20 May 2014

Primary endpoint
25 April 2017

26 July 2023

Quick facts

Lead sponsor	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	34
Start date	20 May 2014
Primary completion	25 April 2017
Estimated completion	26 July 2023
Sites	2 locations across United States

Drugs / interventions tested

• Simvastatin (simvastatin) — full drug profile →
• Doxorubicin/cyclophosphamide

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →
• Stage I Breast Cancer — all drugs for Stage I Breast Cancer →
• Stage II Breast Cancer — all drugs for Stage II Breast Cancer →
• Stage III Breast Cancer — all drugs for Stage III Breast Cancer →

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — full company profile →

Who can join

18 and older, female only, with Breast Cancer or Stage I Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Echocardiographic Global Longitudinal Strain (GLS) Primary · up to 15 weeks

To compare the absolute change in echocardiographic GLS (Global Longitudinal Strain) from baseline (T0) to 2-3 weeks after (T2) completion of 4 cycles of (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who do and do not receive concurrent simvastatin therapy

Group	Value	95% CI
Simvastatin	0.42	± 2.46
No Drug	1.11	± 3.67

Number of Participants With Adverse Events as a Measure of Safety and Tolerability Secondary · 52 weeks

Number of participants with concurrent administration of simvastatin with (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who experience adverse events as defined by NCI CTCAE v4.0.

Group	Value	95% CI
Simvastatin	15

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 30 days after last dose of simvastatin, up to 1 year. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Simvastatin

Serious: 1/15 (7%)

Deaths: 1/15

No Drug

Serious: 0

Deaths: 0

Serious adverse events (1 terms)

Reaction	System	Simvastatin	No Drug
CPK increased	Investigations	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Simvastatin	No Drug
Alanine aminotransferase increased	Investigations	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Generalized Edema	General disorders	—	—
Fatigue	General disorders	—	—
Constipation	Gastrointestinal disorders	—	—

Most-reported serious reactions: CPK increased.

Data from ClinicalTrials.gov NCT02096588 adverse events section.

Sponsor's own description

Doxorubicin (Adriamycin), one of the drugs commonly used for the treatment of breast cancer, is in a class of medications called anthracyclines. Anthracyclines may cause heart damage that can lead to weakening of the heart muscle. This heart damage may happen right away or may occur many years after the anthracycline is given

Simvastatin is an oral medication approved by the FDA to lower cholesterol. Simvastatin is in a class of medications called statins. Some research has shown that statins may prevent heart damage that can be caused by anthracyclines like Doxorubicin (Adriamycin).

The purpose of this study is to determine if taking simvastatin while receiving the chemotherapy Doxorubicin (Adriamycin) will minimize damage to the heart.

This study is for women who will be receiving the anthracycline doxorubicin (Adriamycin) as part of their breast cancer treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).
   de Boer RA, Hulot JS, Tocchetti CG, Aboumsallem JP, et al · · 2020 · cited 134× · PMID 33094495 · DOI 10.1002/ejhf.2029
2. Cardioprotective strategies to prevent breast cancer therapy-induced cardiotoxicity.
   Padegimas A, Clasen S, Ky B. · · 2020 · cited 62× · PMID 30745071 · DOI 10.1016/j.tcm.2019.01.006
3. Cardio-oncology: an overview on outpatient management and future developments.
   Teske AJ, Linschoten M, Kamphuis JAM, Naaktgeboren WR, et al · · 2018 · cited 29× · PMID 30141030 · DOI 10.1007/s12471-018-1148-7
4. Mutant p53, the Mevalonate Pathway and the Tumor Microenvironment Regulate Tumor Response to Statin Therapy.
   Pereira M, Matuszewska K, Glogova A, Petrik J. · · 2022 · cited 17× · PMID 35884561 · DOI 10.3390/cancers14143500
5. Cardioprotection strategies for anthracycline cardiotoxicity.
   Moreno-Arciniegas A, Cádiz L, Galán-Arriola C, Clemente-Moragón A, et al · · 2025 · cited 16× · PMID 39249555 · DOI 10.1007/s00395-024-01078-6
6. Novel Effects of Statins on Cancer via Autophagy.
   Mengual D, Medrano LE, Villamizar-Villamizar W, Osorio-Llanes E, et al · · 2022 · cited 15× · PMID 35745567 · DOI 10.3390/ph15060648
7. Protecting the heart in cancer therapy.
   Finet JE, Tang WHW. · · 2018 · cited 14× · PMID 30345014 · DOI 10.12688/f1000research.15190.1
8. The Potential Therapeutic Application of Simvastatin for Brain Complications and Mechanisms of Action.
   Vuu YM, Kadar Shahib A, Rastegar M. · · 2023 · cited 13× · PMID 37513826 · DOI 10.3390/ph16070914