ANZCTR - Registration

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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

9/02/2024

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]

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

Condition category

Condition code

Cancer

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]

Diagnosis / Prognosis

Comparator / control treatment

None, PROSPECT is a single arm study.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

At 5 years after definitive surgery

Secondary outcome [1]

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]

At 10 years after definitive surgery.

Secondary outcome [2]

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]

At 5 and 10 years after definitive surgery.

Secondary outcome [3]

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]

At 5 and 10 years after definitive surgery.

Secondary outcome [4]

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]

At 5 and 10 years after definitive surgery.

Secondary outcome [5]

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]

At 5 and 10 years after definitive surgery

Secondary outcome [6]

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]

At 5 and 10 years after definitive surgery

Secondary outcome [7]

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]

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

Sex

Females

Can healthy volunteers participate?

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

1/04/2011

Actual

30/09/2011

Date of last participant enrolment

Anticipated

31/05/2019

Actual

2/05/2019

Date of last data collection

Anticipated

31/05/2029

Actual

Sample size

Target

200

Accrual to date

Final

200

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment postcode(s) [1]

3050 - Royal Melbourne Hospital

Recruitment postcode(s) [2]

3084 - Heidelberg

Recruitment postcode(s) [3]

3052 - Parkville

Recruitment postcode(s) [4]

2060 - North Sydney

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Breast Cancer Trials

Address [1]

PO Box 283
The Junction NSW 2291

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC

Ethics committee address [1]

Office for Research
PO Royal Melbourne Hospital
Parkville Victoria 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/10/2010

Approval date [1]

27/01/2011

Ethics approval number [1]

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

Prof Bruce Mann

Address

Director of Breast Services
The Royal Women's Hospital
Suite 12, Department of Surgery
Parkville VIC 3052

Country

Australia

Phone

+61 (03) 9347-6301

Fax

[email protected]

Contact person for public queries

Name

Ms Corinna Beckmore

Address

BCT
PO Box 283
The Junction NSW 2291

Country

Australia

Phone

+61 2 4925 5235

Fax

+61 2 4925 3068

[email protected]

Contact person for scientific queries

Name

Prof Bruce Mann

Address

Director of Breast Services The Royal Women's Hospital Suite 12, Department of Surgery Parkville VIC 3052

Country

Australia

Phone

+61 (03) 9347-6301

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Anonymised Individual Patient Data (IPD) collected during the trial. The specific IPD to be shared (e.g. all data, published data, data of primary outcomes) will be as per the submitted research proposal and as assessed as appropriate by BCT.

When will data be available (start and end dates)?

Data will be made available for request after publication of the main/final study results; no end date.

Note that there may be additional circumstances preventing BCT from sharing requested data as outlined in the BCT Data Sharing Guidelines.

Available to whom?

Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Refer to the BCT Data Sharing Guidelines

Available for what types of analyses?

To achieve the aims in the approved proposal. Please refer to BCT Data Sharing Guidelines

How or where can data be obtained?

Subject to approval by Breast Cancer Trials [email protected] (refer to BCT Data Sharing Guidelines).

Please also see https://researchdata.edu.au/a-single-arm-1002-prospect/2836008 for Research Data Australia record.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
18385	Other				BCT Data Sharing Guidelines	335926-(Uploaded-06-12-2023-12-01-23)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	Citations or Other Details
Study results article	Yes	Mann GB, Skandarajah AR, Zdenkowski N, Hughes J, P... [More Details]
Other files	No	Rose, A. Image-guided de-escalation of treatment: ... [More Details]
Other files	No	Mann B. Primary Results of ANZ 1002: Post operativ... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study.	2024	https://dx.doi.org/10.1016/S0140-6736%2823%2902476-5
Dimensions AI	Intraoperative radiotherapy for early breast cancer — insufficient evidence to change practice	2020	https://doi.org/10.1038/s41571-020-00444-2

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically