Register a trial

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06445738




Registration number
NCT06445738
Ethics application status
Date submitted
24/05/2024
Date registered
6/06/2024

Titles & IDs
Public title
Post-operative Radiotherapy Omission in Selected Patients with Early Breast Cancer Trial International VErsion (PROSPECTIVE)
Scientific title
A Two-arm, Non-randomised, Prospective, Multicentre Study Using Magnetic Resonance Imaging (MRI) Findings and Pathology Features to Select Patients with Early Breast Cancer for Omission of Post-operative Radiotherapy
Secondary ID [1] 0 0
BCT 2401
Universal Trial Number (UTN)
Trial acronym
PROSPECTIVE
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Arm A: Radiotherapy Omission
Other interventions - Arm B: Standard Treatment

Experimental: Radiotherapy Omission - Participants with nil, minimal or mild parenchymal enhancement on pre-operative MRI whose pathology meets inclusion/exclusion requirements for omission of post-operative radiotherapy will be allocated to Arm A, unless the participant prefers to receive Standard Treatment (Arm B) or following clinical team recommendation.

Arm A participants will be divided into 2 groups:

* Arm A1: Grade 1 or 2/HER2 negative ("low risk")
* Arm A2: Grade 3 and/or HER2 positive ("high risk")

Active comparator: Standard Treatment - Participants who are found to be ineligible for RT omission on study; includes management of MRI-detected lesions.

Participants with any of:

* Moderate or marked parenchymal enhancement on pre-operative MRI
* A malignant occult lesion identified on MRI; or
* Pathology that does not meet inclusion/exclusion criteria will receive standard multidisciplinary team recommendations to guide treatment. Participants may also be included in Arm B due to their own preference or following clinical team recommendation.


Treatment: Other: Arm A: Radiotherapy Omission
Omission of radiotherapy based on pre-surgical MRI and pathology findings at surgery.

Other interventions: Arm B: Standard Treatment
Ineligible for RT omission on study; includes management of MRI-detected lesions.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up
Timepoint [1] 0 0
Median of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)
Primary outcome [2] 0 0
Ipsilateral Invasive Recurrence Rate (IIRR) in all patients omitting RT at a median of 5 years follow up
Timepoint [2] 0 0
Median of 5 years follow up
Secondary outcome [1] 0 0
Ipsilateral Invasive Recurrence Rate (IIRR) in all patients omitting RT at a median of 10 years follow up
Timepoint [1] 0 0
Median of 10 years follow up
Secondary outcome [2] 0 0
IIRR in higher risk patients omitting RT and the total cohort omitting RT
Timepoint [2] 0 0
Median of 5 years follow up
Secondary outcome [3] 0 0
IIRR in the breast at 5 and 10 years in the entire cohort undergoing pre-operative MRI and ineligible for RT omission
Timepoint [3] 0 0
Median of 5 and 10 years follow up.
Secondary outcome [4] 0 0
IIR in the breast at 5 and 10 years in the entire cohort undergoing pre-operative MRI
Timepoint [4] 0 0
Median of 5 and 10 years follow up
Secondary outcome [5] 0 0
Ipsilateral DCIS recurrence rate in the entire cohort
Timepoint [5] 0 0
Median of 5 and 10 years follow up.
Secondary outcome [6] 0 0
Ipsilateral DCIS and invasive recurrence rate in all cohorts separately and combined
Timepoint [6] 0 0
Median of 5 and 10 years follow up
Secondary outcome [7] 0 0
Regional recurrence rate in all participants
Timepoint [7] 0 0
Median of 5 and 10 years follow up
Secondary outcome [8] 0 0
Distant recurrence rate in all participants
Timepoint [8] 0 0
Median of 5 and 10 years follow up
Secondary outcome [9] 0 0
Contralateral DCIS and invasive breast cancer in each arm separately, and combined
Timepoint [9] 0 0
Median of 5 and 10 years follow up
Secondary outcome [10] 0 0
Breast cancer specific survival rate in all groups separately and combined
Timepoint [10] 0 0
Median of 5 and 10 years follow up
Secondary outcome [11] 0 0
Overall survival rate
Timepoint [11] 0 0
Median of 5 and 10 years follow up
Secondary outcome [12] 0 0
PRO: Fear of Cancer Recurrence
Timepoint [12] 0 0
Median 24 months post-surgery
Secondary outcome [13] 0 0
PRO: HRQoL (functional and aesthetic outcomes)
Timepoint [13] 0 0
24 months post-surgery
Secondary outcome [14] 0 0
PRO: HRQoL (fatigue, body image, financial toxicity)
Timepoint [14] 0 0
24 months post-surgery
Secondary outcome [15] 0 0
PRO: Difference over time in FCR
Timepoint [15] 0 0
From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery
Secondary outcome [16] 0 0
PRO: Difference over time in HRQoL (functional and aesthetic outcomes)
Timepoint [16] 0 0
From allocation to 6-, 12-, 24- and 60 months median follow up post-surgery
Secondary outcome [17] 0 0
PRO: Difference over time in HRQoL (ffatigue, body image, financial toxicity)
Timepoint [17] 0 0
From allocation to 6-, 12-, 24- and 60 months median follow up post-surgery
Secondary outcome [18] 0 0
PRO: Differences in Quality of Life Years (QALYs)
Timepoint [18] 0 0
24 months post-surgery

Eligibility
Key inclusion criteria
For inclusion in the study at Registration, participants must fulfil all of the following criteria:

1. Has provided written, informed consent to participate in the study.
2. Female participants = 50 years old with histologically* confirmed ER-positive and/or HER2-positive invasive breast cancer.
3. In good health and suitable for prolonged follow up with a life expectancy of at least 10 years; willing to be followed up for 10 years.
4. Breast imaging indicating unifocal**, unilateral breast cancer must have been performed before pre-registration.
5. Willing/able to have surgery within 8 weeks of registration or pre-operative MRI, whichever occurs later.
6. Pathology material from index cancer must be available.
7. Have ECOG performance status 0-2.
8. Participants with Grade 3 cancer and/or HER2-positive cancer must agree to comply with systemic treatment recommendations.

* Oestrogen receptor and progesterone receptor status of invasive cancer will be assessed by immunohistochemistry on the diagnostic core biopsy specimen. The IHC results will be reported as percentage of nuclei stained and a score of intensity from negative, weak, intermediate or high staining

* HER2 neu status will be assessed by immunohistochemistry and will be scored as follows46:

* 0 or 1+ (HER2 negative): No staining or membrane staining that is incomplete and is faint/barely perceptible and in = 10% of tumour cells (0); or incomplete membrane staining that is faint/barely perceptible and in > 10% of tumour cells (1+).
* 2+ (equivocal): weak to moderate complete membrane staining observed in > 10% of tumour cells. Must order reflex test (same specimen using ISH) or order a new test (new specimen if available using HIS or ISH).
* 3+ (HER2 positive): Circumferential membrane staining that is complete, intense and in > 10% of tumour cells.
Minimum age
50 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Any one of the following at Registration is regarded as a criterion for exclusion from the study:

1) Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as Any one of the following at Registration is regarded as a criterion for exclusion from the study:

1. Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as = 10% staining on IHC47.
2. Previous ipsilateral in-situ or invasive breast cancer.
3. Participants who have a mastectomy for the index cancer.
4. Lymphovascular invasion.
5. Multifocal/multicentric breast cancer.
6. Distant metastasis at diagnosis.
7. Bilateral breast cancer.
8. Known breast cancer predisposition gene mutation carriers (BRCA 1 or 2, PALB2, CHEK2, ATM, CDK1, p53).
9. Contraindication to MRI scanning.
10. Concurrent illness/conditions which limits life expectancy to 10 years.
11. Inability to give informed consent. 10% staining on IHC47.

2) Previous ipsilateral in-situ or invasive breast cancer. 3) Participants who have a mastectomy for the index cancer. 4) Lymphovascular invasion. 5) Multifocal/multicentric breast cancer. 6) Distant metastasis at diagnosis. 7) Bilateral breast cancer. 8) Known breast cancer predisposition gene mutation carriers (BRCA 1 or 2, PALB2, CHEK2, ATM, CDK1, p53).

9) Contraindication to MRI scanning. 10) Concurrent illness/conditions which limits life expectancy to 10 years. 11) Inability to give informed consent.

Allocation: Arm A - Radiotherapy Omission

In addition to the above criteria, for inclusion in the omission of radiation therapy arm of the study after surgery, participants must fulfil all the following criteria (see Section 9.5.2). Participants not fulfilling any one of the following criterial will be allocated to Arm B:

1. Female participants = 50 years old with histologically* confirmed ER-positive and/or HER2-positive, unifocal**, unilateral invasive breast cancer.
2. Has nil/minimal or mild parenchymal enhancement on pre-operative MRI.
3. Breast conserving surgery with invasive primary tumour (including any surrounding DCIS) = 20 mm.
4. Radial resection margins must be = 2 mm clear of any invasive cancer and = 2 mm clear of any DCIS. 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 (pN0 i+ is eligible for inclusion) by sentinel node biopsy and/or axillary dissection.
6. Absence of lymphovascular invasion and extensive intraductal component.
7. Have no additional BIRADS 3+ lesions not shown to be benign on pre-operative or surgical biopsy.
8. Participants must be allocated within 8 weeks after final breast surgery.

* Oestrogen receptor and progesterone receptor status of invasive cancer will be assessed by immunohistochemistry on the diagnostic core biopsy specimen. The IHC results will be reported as percentage of nuclei stained and a score of intensity from negative, weak, intermediate or high staining

* 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 status. In relation to Allocation 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 = ('Focus A + Focus B + 'the distance between A and B').

Allocation: Arm B - Standard Treatment

In addition to the above Inclusion Criteria, participants who fulfil one any of the following criteria will receive standard treatment:

1. Has moderate or marked parenchymal enhancement on pre-operative MRI.
2. Has a biopsy-proven malignant occult lesion (mOL) identified on MRI.
3. Suspicious lesion identified on CEM but not on MRI and confirmed on investigation to be a malignant lesion.
4. Surgical pathology does not meet the inclusion criteria.
5. Clinical team meeting determination that RT be recommended.
6. Participant chooses to have RT despite being eligible for RT omission.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/01/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2039
Actual
Sample size
Target
1400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
The Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [3] 0 0
Mater Hospital, Sydney - North Sydney
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Monash Cancer Centre (MMC Moorabbin) - Clayton
Recruitment hospital [7] 0 0
The Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2290 - Gateshead
Recruitment postcode(s) [3] 0 0
2060 - North Sydney
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Breast Cancer Trials, Australia and New Zealand
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bruce Mann, MD
Address 0 0
Melbourne Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Heath Badger
Address 0 0
Country 0 0
Phone 0 0
+61 2 4925 5239
Fax 0 0
Email 0 0
heath.badger@bctrials.org.au
Contact person for scientific queries

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.

Supporting document/s available: Study protocol, Analytic code
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.
Available to whom?
Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Applications will be subject to approval by Breast Cancer Trials concept@bctrials.org.au (refer to BCT Data Sharing Guidelines).
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06445738