Plain English Summary
Background and study aims
Preclinical studies support the anticancer activity of statins, however, the existing clinical evidence is inconsistent and not definitive. The aim of this study is to assess the possible cancer chemosensitizing effect of a statin (simvastatin) in metastatic breast cancer (MBC) patients.
Who can participate?
MBC patients undergoing a chemotherapy course of carboplatin and vinorelbine
What does the study involve?
Patients are randomly allocated to receive a 15-day course of either simvastatin or placebo (dummy drug) at day -7 of each chemotherapy cycle. The primary endpoints are objective response rate (ORR) and toxicity, and the secondary endpoint is overall survival (OS).
What are the possible benefits and risks of participating?
Although the beneficial effects of statins in lowering cholesterol are well established, their importance in the area of cancer therapeutics is now gaining greater recognition. At present there is ample evidence to suggest that statins could be used in breast cancer. It provides solid ground for further research on whether statins can improve the efficacy of commonly used cytotoxic agents if given in combination. Possible risks: simvastatin known toxicity.
Where is the study run from?
Al-Baironi Hospital (Syria)
When is the study starting and how long is it expected to run for?
December 2010 to July 2017
Who is funding the study?
Damascus University (Syria)
Who is the main contact?
Prof. Lama Youssef
ylama@hotmail.com
Trial website
Contact information
Type
Scientific
Primary contact
Prof Lama Youssef
ORCID ID
Contact details
International University of Science and Technology
Kiwan Land Campus
Damascus
ylama@hotmail.com
Syria
+963-935-797914
ylama@hotmail.com
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
Damascus University/15073/
Study information
Scientific title
Evaluation of the effects of lipophilic statins on the responsiveness of metastatic breast cancer patients to chemotherapy regimens
Acronym
Study hypothesis
Preclinical studies support the anticancer activity of statins, however, the existing clinical evidence is inconsistent and not definitive. This study aimed at evaluating a postulated cancer chemosensitizing effect of a statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients.
Ethics approval
Approved 26/11/2013, Scientific Research Ethics Committee at the Faculty of Pharmacy, Damascus University (7 Nissan Street, Mazzeh, Damascus, Syria; Tel: +963 (0)112131871), Number: 10
Study design
Prospective single-center randomized double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Metastatic breast cancer
Intervention
Patients were randomly allocated to receive a 15-day course of either simvastatin (40 mg) or placebo at the day -7 of each chemotherapy cycle.
Chemotherapy regimen was conducted every 3 weeks according to the hospital protocol as follows; carboplatin (Carboplatin “Ebewe”), Area under the curve (AUC) 4, intravenously on day 1 and vinorelbine (Navelbine®) intravenously (25 mg/m2) or orally (60 mg/m2) on days 1 and 8 of each cycle. Simvastatin 40 mg or placebo administered orally once daily for 15 days starting at the day -7 of each chemotherapy cycle.
Primary endpoints were objective response rate (ORR) and toxicity, and secondary endpoint was overall survival (OS).
Intervention type
Drug
Phase
Not Applicable
Drug names
Carboplatin, vinorelbine, simvastatin
Primary outcome measure
1. Objective response rate (ORR) calculated based on both complete response + partial response. Patients’ response classified according to the response evaluation criteria in solid tumor (RECIST) (version 1.1) as follows: complete response (CR): complete disappearance of clinical evidence of disease for a minimum of 8 weeks; partial response (PR): decreased in tumor burden ≥30%; stable disease (SD): decreased by <30% or increased by <20%; progressive disease (PD): increase in tumor burden by ≥20%; and non-evaluable response due to specific reasons (e.g., early death or toxicity). To assess tumor progression, physical examination, tumor markers (carcinoembryonic antigen (CEA) and cancer antigen 15–3 (CA15-3)), and radiological studies were conducted at baseline and every three cycles, and bone scan was repeated by the end of the sixth cycle
2. Treatment related-toxicity graded according to the Common Terminology Criteria for Adverse Events, version 4 at each cycle
Secondary outcome measures
Overall survival defined as the time from study entry to death from any cause over the follow-up period (the follow-up lasted until death or the cutoff date of July 2017)
Overall trial start date
28/12/2010
Overall trial end date
01/07/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Female patients attending the breast cancer unit at Al-Baironi Hospital
2. Confirmed diagnosis of metastases (stage IV) prior to commencing chemotherapy course consisting of carboplatin and vinorelbine
3. Age between 20 and 75 years
4. Adequate function of major organs (including cardiac, hepatic and renal functions)
5. ECOG Performance Status score ≤2
Participant type
Patient
Age group
Mixed
Gender
Female
Target number of participants
82
Total final enrolment
82
Participant exclusion criteria
1. Pregnant patients
2. Previous treatment with statins or carboplatin and vinorelbine within 30 days of the study
Recruitment start date
11/08/2011
Recruitment end date
30/07/2012
Locations
Countries of recruitment
Syria
Trial participating centre
Al-Baironi Hospital
Harasta
Damascus
-
Syria
Sponsor information
Organisation
Damascus University
Sponsor details
Baramka
Damascus
-
Syria
+963 (0)11 33923192
info@damascusuniversity.edu.sy
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
Damascus University
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication after registration is completed.
IPD sharing statement
The datasets generated during and/or analysed during the current study are available upon request from Lama A Youssef, B.Pharm, PhD (ylama@hotmail.com).
Intention to publish date
31/12/2019
Participant level data
Available on request
Basic results (scientific)
Publication list