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Trial registered on ANZCTR


Registration number
ACTRN12613000655741
Ethics application status
Approved
Date submitted
15/05/2013
Date registered
14/06/2013
Date last updated
28/01/2020
Date data sharing statement initially provided
28/10/2019
Date results information initially provided
28/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Can the use of low dose radioactive seeds to guide surgical removal of small areas of abnormal breast tissue reduce the rate of second operation compared with standard hook-wire technique? (ROLLIS RCT: Radio-guided Occult Lesion Localisation using Iodine-125 Seeds)
Scientific title
Can Radio-guided Occult Lesion Localisation using Iodine-125 Seeds (ROLLIS) for excision of impalpable breast cancer reduce the rate of pathologically inadequate margins and/or subsequent oncological surgery compared with standard hook-wire localisation? A randomised controlled clinical trial.
Secondary ID [1] 282506 0
Nil
Universal Trial Number (UTN)
U1111-1133-8258
Trial acronym
ROLLIS RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 289161 0
Condition category
Condition code
Cancer 289488 289488 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The radiopharmaceutical product (medical device) is a needle with wax plug, containing a radioactive seed.

I-125 seeds are entered on the Australian Register of Therapeutic Goods for a different purpose (prostate brachytherapy). Low activity seeds are packaged on-site into a sterile needle kit to be used for ROLLIS, under the Therapeutic Goods Administration Clinical Trials Notification scheme.

Participants will give informed consent and be randomised to HWL or ROLLIS.
For ROLLIS participants, a low-dose sterilised radioactive I-125 seed is placed within the patient’s cancer under local anaesthesia with imaging guidance. The approximate duration of the seed insertion procedure is 5 minutes. Localisation by seed may be up to 4 days prior to surgery. The standard 2-view mammogram will be obtained to confirm satisfactory positioning of the seed(s). The seed remains in situ until surgery. If the position of a seed is not ideal, a hook-wire will be inserted to guide the surgical excision. (A second seed may cause confusion rather than aid guidance, since the signal from each seed may not be distinct).
In theatre, the surgeon then uses an intraoperative gamma probe to guide removal of the impalpable cancer containing the seed by breast conserving surgery (BCS) within 4 days.
Intervention code [1] 287158 0
Treatment: Surgery
Intervention code [2] 287159 0
Treatment: Devices
Comparator / control treatment
When an abnormal area in the breast needs to be removed after a needle biopsy (and the surgeon cannot feel it), the current standard method of marking the area for surgical removal is for a radiologist to insert a hook-wire using ultrasound or stereotactic guidance on the day of surgery. This standard intervention is called hook-wire guided localisation (HWL). The approximate duration of HWL is 5 minutes and BCS occurs same day 6 +/- 3 hours. A mammogram is performed to check that hookwire is in a satisfactory position adjacent to the lesion. Occasionally if the position of this hook-wire is not optimal, a second hook-wire may need to be inserted.

Participants will give informed consent and be randomised to HWL or ROLLIS.
For HWL, participants will receive localisation with a standard hook-wire localisation on the morning of surgery followed by BCS on the same day.
Control group
Active

Outcomes
Primary outcome [1] 289587 0
Reduced incidence of unclear margins obtained from pathology reports after BCS
Timepoint [1] 289587 0
1 week post-surgery
Primary outcome [2] 289588 0
Reduced incidence of subsequent oncological surgery obtained from medical records
Timepoint [2] 289588 0
re-excision/mastectomy within 3 months of initial surgery
Secondary outcome [1] 302783 0
Cosmetic assessment of clinical photographs analysed using BCCT.core software
Timepoint [1] 302783 0
1 year post-surgery
Secondary outcome [2] 302784 0
Estimated % breast volume excised (EPBVE) from medical records & pathology records
Timepoint [2] 302784 0
baseline and post-surgery
Secondary outcome [3] 302785 0
Participant self-evaluation will be subjective assessment of cosmesis by validated Body Image Scale (BIS) questionnaire (Hopwood,P et.al.2001)
Timepoint [3] 302785 0
At time of clinical photograph, at least 1 year post- procedure
Secondary outcome [4] 302786 0
Overall cosmetic outcome score out of 12 assessed from 3 outcomes described above
Timepoint [4] 302786 0
1 year post-surgery
Secondary outcome [5] 302787 0
Reduction in unnecessary tissue removal assessed from medical records
Timepoint [5] 302787 0
baseline and post-surgery
Secondary outcome [6] 302788 0
Degree of difficulty/preference for clinicians (Radiologists and Surgeons) assessed by Radiologist's localisation and Surgeon's questionnares developed by us
Timepoint [6] 302788 0
baseline (radiologist) and procedure day (surgeons)
Secondary outcome [7] 302789 0
Post-operative complications will be assessed by a doctor using the Clavien Dindo Classification System for at least 30% of participants. This classification of post-operative complications is the recommended method for assessment by the International Consortium for Health Outcomes Measures.
Timepoint [7] 302789 0
six weeks after procedure
Secondary outcome [8] 302792 0
Participant satisfaction will be assessed by Post - Operative ROLLIS and HWL questionnaires developed by us.
Timepoint [8] 302792 0
2 weeks post-procedure
Secondary outcome [9] 302793 0
Cost benefit analysis to the health system assessed from Diagnoses Related Group (DRG’s) and Patients Assisted Travel Scheme (PATS)
Timepoint [9] 302793 0
end of study
Secondary outcome [10] 302794 0
The cost to improve outcomes will be assessed by review of Diagnoses Related Groups (DRGs) and Patient Assisted Travel Scheme (PATS) to estimate total cost (including; consumables, theatre time, hospital stay).
Timepoint [10] 302794 0
end of study
Secondary outcome [11] 338743 0
Accuracy of placement of device used for lesion localisation will be assessed through the distance between middle of seed / middle of thickened segment of hook-wire and middle of lesion.
Timepoint [11] 338743 0
Baseline (day of localisation)

Eligibility
Key inclusion criteria
•Women 18 years or over.
•Histologically confirmed invasive or in-situ carcinoma that is impalpable or poorly palpable (such that preoperative localisation is considered to be warranted by the treating surgeon),
•Candidate for breast conserving surgery (BCS), based on clinical and radiological evaluation. Pleomorphic LCIS will be included as it is agreed to be of similar significance to Ductal carcinoma in situ (DCIS).
•Completion of a signed and dated written informed consent obtained prior to participation.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
•Male breast cancer - mastectomy is treatment of choice.
•Pregnancy - whilst the radiation dose involved in ROLLIS is very small, the ALARA principle (as low as reasonably achievable) mandates the exclusion.
•Lactation - theoretical possibility of ductal migration of seed.
•More than one separate malignant lesion in the same breast.
•Non-pleomorphic lobular carcinoma in-situ (LCIS) - management remains controversial.

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)
Participants will be recruited from the Breast Centres at Sir Charles Gairdner Hospital (SCGH) and Royal Perth Hospital (RPH), major WA tertiary referral centres for breast cancer treatment. Prior to giving informed consent, eligible women will be given the opportunity to discuss the participant information and consent form with both family and general practitioner. For non-English speaking participants, the services of an official interpreter will be used.
After obtaining informed consent from participants, the following procedure will be used for enrolling a subject and allocating the treatment.
Allocation will involve contacting the holder of the allocation schedule who is “off-site” or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The block randomisation will be done using a database based on the ‘Ralloc’ package within strata. The randomisation will use three randomised block sizes and simple randomisation within blocks to ensure a ratio of experimental (ROLLIS localisation): control (HWL) participants close to unity within strata. The randomisation will use a 2x2x3 design so there are six strata (from two stratification variables). The size and order of the blocks will be randomised.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Nil
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
To detect an absolute 10% improvement in the primary outcome (reduction in incidence of subsequent oncological surgery from 30% to 20%) with a significance level of 5% (two-tailed) and 90% power, a sample size of 293 participants per group will be necessary. To allow for an attrition rate of 10% in each study arm, a total sample of 650 women will be recruited. This estimate of 10% attrition is based on our clinical experience in the RPS and 8.5% attrition observed in the largest published trial (333 participants) of the ROLLIS technique

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 in Australia
Recruitment state(s)
QLD,WA,VIC
Recruitment hospital [1] 1011 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 1012 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 6687 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [4] 6688 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 6689 0
Robina Hospital - Robina
Recruitment hospital [6] 15060 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 6885 0
6000 - Perth
Recruitment postcode(s) [2] 14318 0
6150 - Murdoch
Recruitment postcode(s) [3] 14319 0
3168 - Clayton
Recruitment postcode(s) [4] 14320 0
4226 - Robina
Recruitment postcode(s) [5] 28350 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 9206 0
New Zealand
State/province [1] 9206 0
Hamilton

Funding & Sponsors
Funding source category [1] 287288 0
Government body
Name [1] 287288 0
State Health Research Advisory Council
Address [1] 287288 0
Research Development Unit
Department of Health
PO Box 8172
Perth Business Centre
PERTH WA 6849
Country [1] 287288 0
Australia
Funding source category [2] 297503 0
Charities/Societies/Foundations
Name [2] 297503 0
Ladybird Foundation
Address [2] 297503 0
PO BOX 820
South Perth WA 6951
Country [2] 297503 0
Australia
Primary sponsor type
Individual
Name
Prof Christobel SAUNDERS
Address
M 507, School of Surgery
QEII Medical Centre,
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, Western Australia 6009
Country
Australia
Secondary sponsor category [1] 286040 0
Individual
Name [1] 286040 0
Dr Donna TAYLOR
Address [1] 286040 0
Radiology
Royal Perth Hospital
197 Wellington St
Perth WA 6000
Country [1] 286040 0
Australia
Secondary sponsor category [2] 286041 0
Individual
Name [2] 286041 0
Dr Anita Bourke
Address [2] 286041 0
Breast Centre
Sir Charles Gairdner Hospital
Hospital Ave, Nedlands
Western Australia 6009
Country [2] 286041 0
Australia
Other collaborator category [1] 277401 0
Hospital
Name [1] 277401 0
Sir Charles Gairdner Hospital
Address [1] 277401 0
Hospital Avenue
Nedlands, WA 6009
Country [1] 277401 0
Australia
Other collaborator category [2] 277402 0
Hospital
Name [2] 277402 0
Royal Perth Hospital
Address [2] 277402 0
Wellington Street
Perth, WA 6000
Country [2] 277402 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289264 0
Sir Charles Gairdner Group Human Research Ethics Committee
Ethics committee address [1] 289264 0
Level 2, A Block,
Hospital Avenue
Nedlands, WA 6009
Ethics committee country [1] 289264 0
Australia
Date submitted for ethics approval [1] 289264 0
Approval date [1] 289264 0
10/12/2012
Ethics approval number [1] 289264 0
2012-139
Ethics committee name [2] 289265 0
The Royal Perth Hospital Human Research Ethics Committee House
Ethics committee address [2] 289265 0
Royal Perth Hospital
GPO Box X2213
Perth, WA 6001
Ethics committee country [2] 289265 0
Australia
Date submitted for ethics approval [2] 289265 0
Approval date [2] 289265 0
26/02/2013
Ethics approval number [2] 289265 0
13-032

Summary
Brief summary
This study is comparing the use of low dose radioactive seeds to standard treatment for surgical removal guidance in breast cancer patients.
Who is it for?
You may be eligible to join this study, if you are a female aged 18 years or above and have been diagnosed with breast cancer that is non-palpable (i.e. the surgeon cannot feel it), and thus require a procedure known as localisation.
Trial details: When an abnormal area in the breast needs to be removed after a needle biopsy (and the surgeon cannot feel it), the abnormal area is localised. We are comparing two different localisation techniques in this study. Participants will be randomly (by chance) assigned to one of two techniques. Participants in one group will undergo a procedure known as ROLLILS (radioguided occult lesion localisation and removal of impalpable breast cancers). This involves inserting a low-dose sterilised radioactive iodine seed into the patient's cancer under local anaesthesia with imaging guiding. The patient will then undergo breast conserving surgery within 4 days, during which the surgeon uses the seed to guide removal of the impalpable cancer. Participants in the other group will undergo the standard treatment, known as hook-wire guided localisation (HWL). This is when a hook-wire is placed in the breast on the day of breast conserving surgery by a radiologist. Participants are followed for up to 5 years post-surgery in order to evaluate clinical and cosmetic outcomes, disease recurrence and patient satisfaction. A cost benefit analysis will also be undertaken.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 40058 0
Prof Christobel SAUNDERS
Address 40058 0
M 507, School of Surgery
QEII Medical Centre,
Hospital Avenue,
Nedlands Western Australia 6009
Country 40058 0
Australia
Phone 40058 0
+61 8 9346 2146
Fax 40058 0
Email 40058 0
Christobel.Saunders@uwa.edu.au
Contact person for public queries
Name 40059 0
Dr Donna TAYLOR
Address 40059 0
Radiology
Royal Perth Hospital
197, Wellington St
Perth WA 6000
Country 40059 0
Australia
Phone 40059 0
+61 8 9224 2244
Fax 40059 0
Email 40059 0
Donna.Taylor@health.wa.gov.au
Contact person for scientific queries
Name 40060 0
Dr Donna TAYLOR
Address 40060 0
Radiology
Royal Perth Hospital
197, Wellington St
Perth WA 6000
Country 40060 0
Australia
Phone 40060 0
+61 8 9224 2244
Fax 40060 0
Email 40060 0
Donna.Taylor@health.wa.gov.au)

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary