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Trial registered on ANZCTR


Registration number
ACTRN12610000810011
Ethics application status
Approved
Date submitted
24/09/2010
Date registered
28/09/2010
Date last updated
8/05/2019
Date data sharing statement initially provided
14/01/2019
Date results information initially provided
8/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 1002 PROSPECT - A single arm phase II study using magnetic resonance imaging (MRI) to select patients with early breast cancer for omission of post-operative radiotherapy
Scientific title
ANZ 1002 PROSPECT - Female participants with early breast cancer will have magnetic resonance imaging (MRI) to choose those who can omit having post-operative radiotherapy
Secondary ID [1] 252629 0
ANZ 1002
Universal Trial Number (UTN)
Trial acronym
PROSPECT (Post-operative Radiotherapy Omission in Selected Patients with Early breast Cancer Trial )
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 258127 0
Condition category
Condition code
Cancer 258304 258304 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry to select a subset of breast cancer patients in whom radiotherapy can safely be omitted. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years.
Intervention code [1] 257142 0
Diagnosis / Prognosis
Comparator / control treatment
None, PROSPECT is a single arm study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259151 0
Ipsilateral invasive recurrence rate in the breast at 5 years. Ipsilateral invasive recurrence is defined as an invasive or in situ tumour recurrence in any soft tissue of the ipsilateral conserved breast or skin. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years.
Timepoint [1] 259151 0
At 5 years after definitive surgery
Secondary outcome [1] 265478 0
Ipsilateral invasive recurrence rate in the breast at 10 years. Ipsilateral invasive recurrence is defined as an invasive or in situ tumour recurrence in any soft tissue of the ipsilateral conserved breast or skin. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years.
Timepoint [1] 265478 0
At 10 years after definitive surgery.
Secondary outcome [2] 265704 0
Regional recurrence rate. Regional recurrence is defined as a tumour recurrence in the ipsilateral axillary lymph nodes, extranodal soft tissue of the ipsilateral axilla, ipsilateral internal mammary lymph nodes, and/or ipsilateral supraclavicular lymph nodes. Regional recurrence does not include supraclavicular lymph nodes or tumour in the opposite breast. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years.
Timepoint [2] 265704 0
At 5 and 10 years after definitive surgery.
Secondary outcome [3] 265705 0
Distant recurrence rate. Distant recurrence is defined as tumours in all other areas other than thosed defined as a local or regional recurrence. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years.
Timepoint [3] 265705 0
At 5 and 10 years after definitive surgery.
Secondary outcome [4] 265706 0
Contralateral breast cancer. Contralateral breast cancer is defined as invasive or in situ tumour in the opposite breast. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years.
Timepoint [4] 265706 0
At 5 and 10 years after definitive surgery.
Secondary outcome [5] 265707 0
Overall survival rate. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years. Data about the patients current health status, test results and second non-breast primaries will be collected at follow-up visits scheduled for 6 months from 12 to 60 months post final excisional surgery and annually from 6-10yrs.
Timepoint [5] 265707 0
At 5 and 10 years after definitive surgery
Secondary outcome [6] 265708 0
Breast-cancer specific survival rate. Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years. Data about the patients current health status, test results and second non-breast primaries will be collected at follow-up visits scheduled for 6 months from 12 to 60 months post final excisional surgery and annually from 6-10yrs.
Timepoint [6] 265708 0
At 5 and 10 years after definitive surgery
Secondary outcome [7] 304516 0
Ipsilateral DCIS recurrence rate.Magnetic Resonance Imaging (MRI) scans will be performed prior to trial entry. A second MRI scan will be performed at 18months to exclude local recurrence. Each MRI scan has a duration of 30minutes. A mammogram will be performed at 6months and annually thereafter to 10 years. Data about the patients current health status, test results and second non-breast primaries will be collected at follow-up visits scheduled for 6 months from 12 to 60 months post final excisional surgery and annually from 6-10yrs.
Timepoint [7] 304516 0
At 5 and 10 years after definitive surgery

Eligibility
Key inclusion criteria
1. Female patients >=50 years old with histologically confirmed, unifocal*, unilateral invasive breast cancer

2. In good health and suitable for prolonged follow up with a life expectancy of at least 5 years

3. Breast conserving surgery with invasive primary tumour (including any surrounding DCIS) <=20 mm

4. Resection margins must be >= 2 mm clear of any invasive cancer and >=2 mm clear of any DCIS. However, superficial or deep margins of <2 mm for invasive cancer and DCIS are allowed if all breast tissue from the subcutaneous tissue or pectoralis fascia respectively was removed and radial margins are >=2 mm for invasive cancer and DCIS

5. pN0 by sentinel node biopsy and/or axillary dissection

6. Mammogram must have been performed within 3 months prior to first excisional surgery for breast cancer and must show unifocal* breast cancer

7. Pre-operative MRI must be performed after the patient and the investigator sign screening consent and no more than 6 weeks prior to the first excisional surgery for breast cancer

8. Radiological imaging (Ultrasound, Mammogram and MRI) must be made available for central review as part of the quality control measures for this trial. In the event of an interpretation discrepancy between the local site and the central review, the central review interpretation will be used to determine eligibility.

9. Parenchymal enhancement on pre-operative MRI must be defined as nil/minimal or mild. In the event of an interpretation discrepancy between the local site and the central review, the central review interpretation will be used to determine eligibility

10. Pathology material from any ipsilateral recurrence (invasive tumour and/or DCIS) must be available for submission for central review as part of the quality control measures for this trial.

11. ECOG performance status 0-1

12. Written informed consent must be signed and dated by the patient and the investigator prior to registration to the trial

13. Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines

14. Patients must be registered within 8 weeks after final breast surgery and be accessible for long term follow up

15. Patients must cease all hormonal contraceptives and hormone replacement therapies within 4 weeks following histological diagnosis of invasive breast cancer

16. Patients must agree to comply with systemic treatment recommendations (e.g. hormonal therapy for ER+/PR+ tumours, trastuzumab for HER2 positive cancers)

* Where histopathology is unable to identify a ‘bridge’ of tumour tissue joining two or more apparent invasive cancer foci the following will be used to confirm unifocal disease:
- All foci must be of the same histology
- All foci must have the same hormone (ER and PR) and HER2 neu status
- In relation to criteria 3: the overall tumour size (including additional foci of DCIS) must remain <=20 mm. The tumour size is defined as the longest distance between the outer most edges of all foci, the space between the two or more foci is included in the overall size: Size = (‘Foci A + Foci B + ‘the distance between A and B’).
Minimum age
50 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnostic MMG shows prominent calcification in the index lesion.

2. Triple negative cancers (ER-ve and PR-ve and HER2-ve) where ER and PR positivity is defined as >=1% staining on IHC

3. Previous in-situ or invasive breast cancer

4. Patients who have had a mastectomy

5. Extensive DCIS (Extensive Intraductal Component (EIC)). Extensive DCIS is defined as invasive carcinoma with the following three components:
a. DCIS is present within the invasive tumour; and
b. DCIS within invasive tumour comprises more than 25% of the invasive tumour volume; and
c. DCIS exists beyond the margin of the invasive tumour

6. Lymphovascular invasion; Multifocal/multicentric breast cancer; Distant metastasis at diagnosis or bilateral breast cancer

7. HER2 positive patients who will not receive trastuzumab as part of adjuvant systemic therapy

8. Gene carriers (BRCA 1,2) or those whose family history of breast cancer reaches the high-risk category of the Cancer Australia

9. Contraindication to MRI scanning (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m^2, pacemaker, implanted non MRI compatible devices, cochlear implants, neurostimulators, insulin infusion pumps, pregnancy or lactation)

10. Moderate or marked background parenchymal enhancement on pre-operative MRI. In the event of an interpretation discrepancy between the local site and the central review, the central review interpretation will be used to determine eligibility.

11. Concurrent illness/conditions which limits life expectancy to 5 years

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)
Patients will be recruited from investigators clinical practices. Patients will sign a 'consent to screen' form at the pre-registration step. A separate written consent form must also be signed by the patient and investigator prior to registration.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Nil
Phase
Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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)
NSW,VIC
Recruitment postcode(s) [1] 8426 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [2] 8427 0
3084 - Heidelberg
Recruitment postcode(s) [3] 8428 0
3052 - Parkville
Recruitment postcode(s) [4] 8429 0
2060 - North Sydney

Funding & Sponsors
Funding source category [1] 257657 0
Other Collaborative groups
Name [1] 257657 0
Breast Cancer Trials
Address [1] 257657 0
PO Box 283
The Junction NSW 2291
Country [1] 257657 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Breast Cancer Trials
Address
PO Box 283
The Junction NSW 283
Country
Australia
Secondary sponsor category [1] 256873 0
None
Name [1] 256873 0
Address [1] 256873 0
Country [1] 256873 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297074 0
Melbourne Health HREC
Ethics committee address [1] 297074 0
Office for Research
PO Royal Melbourne Hospital
Parkville Victoria 3050
Ethics committee country [1] 297074 0
Australia
Date submitted for ethics approval [1] 297074 0
10/10/2010
Approval date [1] 297074 0
27/01/2011
Ethics approval number [1] 297074 0
2010.097

Summary
Brief summary
This study aims to determine if some women with early breast cancer can avoid radiotherapy treatment after breast surgery. If radiotherapy treatment can be omitted without there being any more than a very small risk of the cancer coming back in the same breast, more women may be able to avoid radiotherapy in the future. This means that these women would avoid 5 weeks of daily radiotherapy and the possible short term side effects; including, fatigue, skin redness, discomfort. Radiotherapy is associated with long term side effects which also may be avoided: discomfort in the breast, thickening of breast tissue, and very occasionally possible lung problems (pneumonitis and lung scarring), heart problems and a very small risk of radiation-induced cancer.

Who is it for?
This study is for women with early breast cancer that must be positive for the oestrogen receptor and/or progesterone receptor and/or human epidermal growth factor receptor. Prior to entering the main study, patients must have a magnetic resonance imaging (MRI) scan. All treatment is standard treatment except that radiotherapy after surgery to remove the breast cancer will not be given.

Trial Details
The study will use magnetic resonance imaging (MRI) to select women with early breast cancer for whom radiotherapy is not needed because the risk of a local recurrence (cancer coming back in the same area) is low. We are investigating whether the abnormalities found by MRI are in fact the reason that local recurrence sometimes occurs, so if nothing is found on MRI, radiotherapy may not be required.
Trial website
www.breastcancertrials.org.au
Trial related presentations / publications
Public notes
Breast Cancer Trials formerly known as the Australia & New Zealand Breast Cancer Trials Group.

Contacts
Principal investigator
Name 31604 0
Prof Bruce Mann
Address 31604 0
Director of Breast Services
The Royal Women's Hospital
Suite 12, Department of Surgery
Parkville VIC 3052
Country 31604 0
Australia
Phone 31604 0
+61 (03) 9347-6301
Fax 31604 0
Email 31604 0
bruce.mann@mh.org.au
Contact person for public queries
Name 14851 0
Ms Corinna Beckmore
Address 14851 0
BCT
PO Box 283
The Junction NSW 2291
Country 14851 0
Australia
Phone 14851 0
+61 2 4925 5235
Fax 14851 0
+61 2 4925 3068
Email 14851 0
corinna.beckmore@bctrials.org.au
Contact person for scientific queries
Name 5779 0
Prof Bruce Mann
Address 5779 0
Director of Breast Services The Royal Women's Hospital Suite 12, Department of Surgery Parkville VIC 3052
Country 5779 0
Australia
Phone 5779 0
+61 (03) 9347-6301
Fax 5779 0
Email 5779 0
bruce.mann@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data Sharing process for this study is in development and will be updated as soon as it is available.
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