Condition category
Cancer
Date applied
24/09/2019
Date assigned
11/10/2019
Last edited
11/10/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results overdue

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

http://damascusuniversity.edu.sy

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

Publication citations

Additional files

Editorial Notes

11/10/2019: Trial's existence confirmed by ethics committee.