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Trial registered on ANZCTR


Registration number
ACTRN12613000253707
Ethics application status
Approved
Date submitted
21/02/2013
Date registered
4/03/2013
Date last updated
13/03/2020
Date data sharing statement initially provided
4/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
TROG 12.02: Positron Emission Tomography (PET) Scans for Locally Advanced Breast Cancer and Diagnostic Magnetic Resonance Imaging (MRI) to Determine the Extent of Operation and Radiotherapy
Scientific title
TROG 12.02 PET Scans for Locally Advanced Breast Cancer and Diagnostic MRI to Determine the Extent of Operation and Radiotherapy
Secondary ID [1] 281766 0
NIL
Universal Trial Number (UTN)
Trial acronym
PET LABRADOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Breast Cancer 288083 0
Condition category
Condition code
Cancer 288456 288456 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The use of the medical imaging techniques of Breast Magnetic Resonance Imaging (MRI) and Positron emission tomography -computed tomography (PET-CT).
MRI and PET-CT will be taken upto 4 times during the study, pre treatment, between 4 to 5 weeks from start of primary systemic treatment, between 3-5 weeks after primay systemic treament is completed and if applicable for inoperable participants, between 10-12 weeks after from radiotherapy treatment.
Each MRI scan will take 20-40 minutes to complete. Each PET-CT takes 60-90 minutes to complete.
Intervention code [1] 286311 0
Treatment: Devices
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288622 0
The primary objective of the study is to demonstrate a local recurrence rate of < or = 20% at three years in patients who undergo Breast Conserving Surgery (BCS) based on histopathology, MRI and PET-CT scans.
Timepoint [1] 288622 0
Three and Five years post registration
Secondary outcome [1] 300619 0
To determine the accuracy of breast MRI and a PET-CT scan to detect the extent of disease within the breast and regional nodes at diagnosis. This is determined by the presence of disease in the breast and nodes on pre-treatment biopsies and pathology of definitive surgical specimen.
Timepoint [1] 300619 0
Operability Assesment and at Surgery
Secondary outcome [2] 300620 0
To determine the accuracy of initial tumour response measurement by criteria breast MRI and a PET-CT scan as a predictor of pathological response to Primary Systemic Therapy (PST) by the response on biopsies performed and changes in MRI and PET-CT scan (according to RECIST and EORTC criteria).
Timepoint [2] 300620 0
Clinical Exam: Between week 4-5 after start of PST and between week 3-5 from last PST

Biopsy; Between week 4-5 after start of PST and between week 3-5 from last PST

Imaging Assesments; Pre Treatment, between week 4-5 after start of PST and between week 3-5 from last PST
Secondary outcome [3] 300621 0
To determine the accuracy of a PET-CT scan to detect distant metastases compared with bone scan and CT scan head / chest / abdomen / pelvis, and histopathology of any lesions biopsied as the reference standard to verify additional findings detected by PET-CT scan.
Timepoint [3] 300621 0
Imaging Assesments;
CT Scan - Pre Registration
PET CT - Pre Treatment, between week 4-5 after start of PST and between week 3-5 from last PST, 12 weeks after last radiation treatment, annually from the date of registration.
Secondary outcome [4] 300622 0
To determine the success rate and accuracy of Sentinel node biopsy after PST by sentinal node study and hisptopathologicial presence.
Timepoint [4] 300622 0
Time of definitive breast surgery
Secondary outcome [5] 300623 0
To document Disease Free Survival for all patients.
Timepoint [5] 300623 0
Imaging Assesments; Pre-Treatment, between week 4-5 after start of PST, between week 3-5 from last PST, 12 weeks after last radiation treatment and annually from the date of registration
Secondary outcome [6] 300624 0
To correlate local and regional relapses with Radiation Therapy parameters (fields, volumes and doses).
Timepoint [6] 300624 0
On replapse
Secondary outcome [7] 300625 0
To document and compare QoL (including body image) for women undergoing either BCS, mastectomy or RT over time using EORTC QLQ-C30 and QLQ-BR23
Timepoint [7] 300625 0
1. Pre-treatment (within 21 days of registration and before first day of systemic therapy).
2. On the day of last PST, when the cumulative effects of PST are likely to be maximal.
3. Between 3-5 weeks after the last cycle of PST when most of the acute effects of systemic therapy should have resolved.
4. On the day of discharge from breast surgery, when symptoms are likely to be maximal.
5. Four weeks after the last surgical procedure, when acute post-operative symptoms are expected to have resolved.
6. On the day of last Radiation Treatment, when the effects will be at their nadir.
7. Two weeks after the last Radiation Treatment, when acute radiation effects are expected to have resolved.
8. 12 weeks after the last RT, when sub-acute side effects are expected to have resolved.
9. Annually from the date of registration for 5 years, to detect a change in QoL over time.
Secondary outcome [8] 300626 0
To document the cosmetic outcome for women - measured objectively with digital photographs and subjectively with the EORTC Cosmetic Rating System (clinician rated) and the Breast Cancer Treatment Outcome Scale (patient rated)
Timepoint [8] 300626 0
Pre-treatment, between 3-5 weeks from the last day of PST, 4 weeks post surgery, 12 weeks after last radiation and annually post-treatment for patients who have had BCS and those who did not have surgery.
Secondary outcome [9] 300627 0
To document and compare lymphoedema rates for women undergoing BCS, mastectomy or RT (presence or absence, and grade (AECTC v4.0) when present)
Timepoint [9] 300627 0
pre-treatment, between week 3 and 5 from last PST, 4 weeks post-operatively, Week 12 post-radiation, and annually from the date of registration
Secondary outcome [10] 300628 0
To document patients’, medical oncologist’s and surgeons’ decisions about treatment
a. changing PST at between week 4-5 from day of first PST, and whether this decision is based on conventional tests and/or MRI-PET-CT.
b. BCS or mastectomy recorded at between week 3-5 from the last PST, and whether this decision is based on information from the conventional tests and/or from MRI/PET-CT.
Timepoint [10] 300628 0
Between week 4-5 from day of first PST and between week 3-5 from the last PST
Secondary outcome [11] 300629 0
To document the costs of including breast MRI + / - PET-CT in the management strategy of women with large or locally advanced breast cancer (LABC) treated by PST (The type and number of additional/changed resource use associated with MRI/PET findings, and unit cost of each resource based on Medical Benifit Scheme, Pharmaceutical Benifits Scheme and hospital billing data)
Timepoint [11] 300629 0
End of study
Secondary outcome [12] 300630 0
To assess the cost consequences of BCS rather than mastectomy (based on MBS, PBS and hospital billing data)
Timepoint [12] 300630 0
End of study
Secondary outcome [13] 300631 0
To obtain a bio-bank of tumour and serum samples.
Timepoint [13] 300631 0
1. Pre-treatment
2. Between week 4-5 after the start of PST and if inoperable breast tumour bewtween week 3-5 after the last PST
3. At the time of definitive breast surgery.

Eligibility
Key inclusion criteria
1. Cytological + / - Histological confirmation of disease within 28 days prior to registration
2. Clinical Stage III (non-inflammatory) unilateral breast cancer
3. Adequate haematological, renal and hepatic function as defined by:
a) Absolute neutrophil count (ANC, segs + bands) > / =1.5 x 109 / L
b) Platelet count > / = 100 x 109 / L
c) Total Bilirubin > / = 1.5 x upper normal limit
d) Alaninie aminotransferase (ALT) < / = 2.5 x upper normal limit
e) EGFR >30ml/min
4. Women must be suitable for radical treatment employing chemotherapy, surgery, radiation therapy + / - trastuzumab + / - hormonal therapy
5. A ECOG performance status score of 1 or less within 28 days prior to registration
6. No contraindications to receiving radiation treatment
7. Life expectancy greater than 36 months
8. Participants capable of childbearing are using adequate contraception.
9. Available for follow up

Patients may proceed to protocol treatment if they meet the following criteria:
10. Adequate cardiac function as defined by a left ventricular ejection fraction of >50%, unless patient is enrolled on a study of primary endocrine therapy.
11. Patients who have no metasteses on PET CT scan OR PET-CT scan identifies up to 3 sites of metastases only.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant or lactating
2. Women who are unwilling to have photographs taken of the area from the mid-neck to navel at specified time-points throughout the study.
3. Women with implanted medical or electronic devices deemed by the MRI radiologist to be a contra-indication to performing a breast MRI, for example: implanted defibrillator, cardiac pacemaker, a cochlear implant, implanted drug infusion port, a metallic joint prosthesis, nerve stimulators, metal pins, screws, plates, stents or surgical staples
4. Clinical evidence of bilateral breast cancer
5. Previous RT to the area to be treated
6. Previous chemotherapy
7. Previous surgery to the ipsilateral breast or nodes
8. Previous contralateral breast cancer
9. Prior diagnosis of cancer with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10% within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix
10. Patients with clinical evidence of metastatic disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a non randomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Quasi-experimental
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary endpoint will be reported as the proportion of patients undergoing BCS who have experienced a LR, together with the 90% confidence interval. Time-to-event outcomes
will be described using Kaplan Meier curves as appropriate. Exploratory analyses (both univariate and multivariate) will be performed using appropriate statistical methods (chisquared
test, logistic, linear and proportional hazards regression). No adjustment will be made for multiple comparisons and the significance level for comparisons will be set at a nominal 5% level.

Responses to all patient-reported QoL outcome measures will be scored as per each instrument’s standard scoring algorithm and analysed with linear mixed models, which account for correlation across repeated measures. These models will be used to describe the time course of impacts and to assess whether the time course differs between groups (BCS or mastectomy) by testing the group by time interaction.

Costs will be measured from a health system perspective. In addition to documenting the costs of the MRI and PET-CT scans used to determine operability, the consequences of the
imaging results on patient management will be recorded and costed including the number and type of additional test, procedures, consultations and treatments received or avoided as a direct consequence of the imaging findings.

Recruitment
Recruitment status
Recruiting
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)
ACT,NSW,NT,QLD
Recruitment hospital [1] 4175 0
Westmead Hospital - Westmead
Recruitment hospital [2] 4176 0
The Canberra Hospital - Garran
Recruitment hospital [3] 4177 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 4178 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 4179 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 10085 0
2145 - Westmead
Recruitment postcode(s) [2] 10086 0
2605 - Garran
Recruitment postcode(s) [3] 10087 0
2170 - Liverpool
Recruitment postcode(s) [4] 10088 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 10089 0
0810 - Tiwi
Recruitment outside Australia
Country [1] 4790 0
New Zealand
State/province [1] 4790 0

Funding & Sponsors
Funding source category [1] 286552 0
Hospital
Name [1] 286552 0
Radiation Oncology Network (Westmead & Nepean Hospitals)
Address [1] 286552 0
Crown Princess Mary Cancer Centre Westmead
Nepean Cancer Care Centre
PO Box 533
Wentworthville
NSW 2145
Country [1] 286552 0
Australia
Primary sponsor type
Other Collaborative groups
Name
TROG
Address
TROG Central Office
PO Box 88
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 285340 0
None
Name [1] 285340 0
Address [1] 285340 0
Country [1] 285340 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288847 0
Western Sydney Local Health District
Ethics committee address [1] 288847 0
Research Office
Westmead Hospital
Rm 2020
Clinical Sciences Building
WESTMEAD NSW 2145
Ethics committee country [1] 288847 0
Australia
Date submitted for ethics approval [1] 288847 0
04/03/2013
Approval date [1] 288847 0
16/09/2013
Ethics approval number [1] 288847 0

Summary
Brief summary
The primary purpose of this study is to investigate whether breast MRI and a PET-CT scan can accurately predict which women with locally advanced breast cancer (LABC) treated by initial Primary Systemic Treatment (PST), can undergo Breast Conserving Surgery (BCS), without compromising local control or Disease Free Survival.

You may be eligible to join this study if you are over 18 years old, female, with Clinical Stage III (non-inflammatory) unilateral breast cancer.

All patients receive PST as per local practice before operability is then assessed. MRI and PET-CT scan will be taken up to four times during the study; 1/pre-treatment, 2/between 4 and 5 weeks from start of PST, 3/between 3 and 5 weeks after PST is completed and 4/between 10 and12 weeks after radiotherapy treatment (for participants that are inoperable). Each MRI scan will take 20-40 minutes to complete. Each PET-CT takes 60-90 minutes to complete.
* If LABC becomes operable, either mastectomy or BSC is performed as well as Sentinal Node Biopsy (SNB) and axillary node dissection. All patients receive radiotherapy 6-8 weeks post-operatively.
* If LABC remains inoperable, radiotherapy is given to the breast and nodes. 5-7 weeks after completion of radiotherapy and the patient is re-assessed. If disease has become operable, mastectomy and axillary node dissection is performed.
* All patients with a hormone sensitive tumour commence hormonal therapy 14 days after the completion of treatment to the breast and nodes.

This study aims to find out if women with LABC can have BCS instead of mastectomy with a low chance of the cancer returning.
Trial website
https://trog.com.au/TROG-1202-PET-LABRADOR
Trial related presentations / publications
NIL
Public notes
NIL

Contacts
Principal investigator
Name 37018 0
A/Prof Verity Ahern
Address 37018 0
Radiation Oncology Network
The Crown Princess Mary Cancer Centre
Westmead Hospital
PO Box 533, Wentworthville,
NSW 2145
Country 37018 0
Australia
Phone 37018 0
+61 02 8890 5200
Fax 37018 0
Email 37018 0
verity.ahern@health.nsw.gov.au
Contact person for public queries
Name 37019 0
Ms Tracy Pearl-Larson
Address 37019 0
Radiation Oncology Network
The Crown Princess Mary Cancer Centre
Westmead Hospital,
PO Box 533, Wentworthville,
NSW 2145,
Country 37019 0
Australia
Phone 37019 0
+61 02 8890 5254
Fax 37019 0
+61 (02) 9891 5814
Email 37019 0
tracy.pearl-larson@health.nsw.gov.au
Contact person for scientific queries
Name 37020 0
Dr Verity Ahern
Address 37020 0
Radiation Oncology Network
The Crown Princess Mary Cancer Centre
Westmead Hospital
PO Box 533, Wentworthville,
NSW 2145
Country 37020 0
Australia
Phone 37020 0
+61 02 8890 5200
Fax 37020 0
Email 37020 0
verity.ahern@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
No Results