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Trial registered on ANZCTR


Registration number
ACTRN12612000662864
Ethics application status
Approved
Date submitted
19/06/2012
Date registered
20/06/2012
Date last updated
20/05/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Does the use of simvastatin reduce side effects in patients receiving radiation for breast cancer?
Scientific title
Randomised, controlled phase II trial of simvastatin as prophylaxis against radiation–induced skin toxicity in breast cancer patients
Secondary ID [1] 280703 0
Nil
Universal Trial Number (UTN)
U1111-1131-9673
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer 286741 0
Condition category
Condition code
Cancer 287042 287042 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Simvastatin 40 mg daily orally during period of radiation treatment and for 3 weeks afterwards. The duration of radiation may vary between patients.
Intervention code [1] 285121 0
Treatment: Drugs
Comparator / control treatment
Non-intervention control (patients receiving radiation but no study medication). The duration of radiation may vary between patients.
Control group
Active

Outcomes
Primary outcome [1] 287375 0
Incidence of grade 2 or greater acute radiation-related skin toxicity, assessed clinically using the modified RTOG acute skin toxicity scoring scale.
Timepoint [1] 287375 0
Weekly during radiation treatment and at 2 weeks and 6-12 weeks after completion of radiation.
Secondary outcome [1] 298027 0
Time to onset of grade 2 or greater acute skin toxicity, assessed clinically (visually) using the modified RTOG acute radiation skin toxicity scale.
Timepoint [1] 298027 0
Weekly during radiation treatment and at 2 weeks and 6-12 weeks after completion of radiation.
Secondary outcome [2] 298028 0
The proportion of patients requiring additional topical treatment, assessed clinically
Timepoint [2] 298028 0
Weekly during radiation treatment and at 2 weeks and 6-12 weeks after completion of radiation.
Secondary outcome [3] 298029 0
Compliance with the trial medication, assessed clinically
Timepoint [3] 298029 0
Weekly during radiation treatment and at 2 weeks and 6-12 weeks after completion of radiation.
Secondary outcome [4] 298030 0
Statin-related toxicities, assessed by patient questionnaire
Timepoint [4] 298030 0
Weekly during radiation treatment and at 2 weeks and 6-12 weeks after completion of radiation.
Secondary outcome [5] 298031 0
Subjective radiation-related toxicities, assessed by patient questionnaire
Timepoint [5] 298031 0
Weekly during radiation treatment and at 2 weeks and 6-12 weeks after completion of radiation.

Eligibility
Key inclusion criteria
Patients with resected invasive cancer or carcinoma in-situ of the breast treated with either breast-conserving surgery or mastectomy who are planned to receive adjuvant radiation therapy.

Radiation fields may include the breast, chest wall, supraclavicular and/or axillary regions. Acceptable dose fractionation schedules include 50Gy in 25 fractions, 45Gy in 20 fractions, 42.5Gy in 16 fractions or 40Gy in 15 fractions, with or without a boost.

Patients may be taking adjuvant hormonal therapy and/or trastuzumab for breast cancer

Patients may have received prior adjuvant chemotherapy

Patients have given written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients receiving other hypofractionated radiation schedules

Patients requiring the use of skin bolus with their radiotherapy

Patients with pre-existing ulceration, infection or skin rashes within the radiation treatment field

Known contra-indication to statins including hypersensitivity, active liver disease or unexplained persistent elevation of transaminases, concomitant administration of potent CYP3A4 inhibitors

Concurrent chemotherapy

Patients currently on statins or taken within the last 6 weeks

Current pregnancy or breast-feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible, consented patients will be registered including details of three stratification factors for randomisation: surgery (breast conserving surgery vs mastectomy), planned use of boost or not, and fraction size (2.0 Gy or less vs >2.0 Gy). The completed request for randomisation will be given to the hospital pharmacy who will allocate patients to treatment based on the stratification group they fall into, in a double-blinded fashion, using numbered opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random allocation of patients in a 1:1 ratio within the strata will be undertaken via a computerised method.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4372 0
New Zealand
State/province [1] 4372 0

Funding & Sponsors
Funding source category [1] 285471 0
Charities/Societies/Foundations
Name [1] 285471 0
Waikato Medical Research Foundation
Address [1] 285471 0
Waikato Hospital
Pembroke Street
Hamilton 3240
Country [1] 285471 0
New Zealand
Funding source category [2] 285472 0
Hospital
Name [2] 285472 0
Waikato District Health Board
Address [2] 285472 0
Pembroke Street
Hamilton 3240
Country [2] 285472 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato District Health Board
Address
Pembroke Street
Hamilton 3240
Country
New Zealand
Secondary sponsor category [1] 284324 0
None
Name [1] 284324 0
Address [1] 284324 0
Country [1] 284324 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287484 0
Northern Y Regional Ethics Committee
Ethics committee address [1] 287484 0
C/o Ministry of Health
PO Box 1031
Hamilton 3240
Ethics committee country [1] 287484 0
New Zealand
Date submitted for ethics approval [1] 287484 0
11/06/2012
Approval date [1] 287484 0
22/08/2012
Ethics approval number [1] 287484 0
NTY/12/06/046

Summary
Brief summary
Skin injury is a common side effect of breast-cancer radiation therapy. Radiation-induced skin toxicity is a common clinical problem that affects approximately 95% of women receiving breast radiation. Skin reactions range from redness to extensive superficial ulcers. Severe skin reactions can be painful, and may result in treatment interruptions or dose reduction, with reduced effectiveness of treatment.
Over the years, there have been many trials looking at the various skin care products that are currently in use, but to date none of these have been proven to prevent radiation-induced toxicity. Recently laboratory studies have reported that use of statins (a group of cholesterol-lowering drugs) can reduce radiation-induced inflammatory reactions. They might also reduce the risk of breast cancer recurrence.
We are performing this study to see if statins (in this case simvastatin) can reduce the inflammation from radiation in breast cancer patients. We will give 65 patients simvastatin 40mg daily during radiation treatment and for 3 weeks afterwards; 65 patients will get placebo (a dummy pill). A doctor will assess the skin inflammation each week during treatment and several weeks after finishing radiation and patients will also rate any symptoms and side effects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34338 0
Dr Shibu Joseph
Address 34338 0
Regional Cancer Centre Waikato Hospital Pembroke Street Hamilton 3240
Country 34338 0
New Zealand
Phone 34338 0
+64 7 839 8899
Fax 34338 0
+64 7 839 8778
Email 34338 0
shibu.joseph@waikatodhb.health.
Contact person for public queries
Name 17585 0
Dr Dr Shibu Joseph
Address 17585 0
Regional Cancer Centre
Waikato Hospital
Pembroke Street
Hamilton 3240
Country 17585 0
New Zealand
Phone 17585 0
+64 7 839 8899
Fax 17585 0
+64 7 839 8778
Email 17585 0
shibu.joseph@waikatodhb.health.nz
Contact person for scientific queries
Name 8513 0
Dr Dr Michael Jameson
Address 8513 0
Regional Cancer Centre
Waikato Hospital
Pembroke Street
Hamilton 3240
Country 8513 0
New Zealand
Phone 8513 0
+64 7 839 8899
Fax 8513 0
+64 7 839 8778
Email 8513 0
michael.jameson@waikatodhb.health.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary