Evaluation of the effects of simvastatin in metastatic breast cancer patients
| ISRCTN | ISRCTN12964275 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12964275 |
| Secondary identifying numbers | Damascus University/15073/ |
- Submission date
- 24/09/2019
- Registration date
- 11/10/2019
- Last edited
- 02/09/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
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
Contact information
Scientific
International University of Science and Technology
Kiwan Land Campus
Damascus
ylama@hotmail.com
Syria
| Phone | +963-935-797914 |
|---|---|
| ylama@hotmail.com |
Study information
| Study design | Prospective single-center randomized double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Evaluation of the effects of lipophilic statins on the responsiveness of metastatic breast cancer patients to chemotherapy regimens |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 28/12/2010 |
| Completion date | 01/07/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Female |
| Target number of participants | 82 |
| Total final enrolment | 82 |
| Key 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 |
| Key exclusion criteria | 1. Pregnant patients 2. Previous treatment with statins or carboplatin and vinorelbine within 30 days of the study |
| Date of first enrolment | 11/08/2011 |
| Date of final enrolment | 30/07/2012 |
Locations
Countries of recruitment
- Syria
Study participating centre
Damascus
-
Syria
Sponsor information
University/education
Baramka
Damascus
-
Syria
| Phone | +963 (0)11 33923192 |
|---|---|
| info@damascusuniversity.edu.sy | |
| Website | http://damascusuniversity.edu.sy |
"ROR" |
https://ror.org/03m098d13 |
Funders
Funder type
University/education
No information available
Results and Publications
| Intention to publish date | 31/12/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication after registration is completed. |
| IPD sharing plan | 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). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 10/08/2020 | 02/09/2020 | Yes | No |
Editorial Notes
02/09/2020: Publication reference added.
11/10/2019: Trial's existence confirmed by ethics committee.
