Post-operative Radiotherapy Omission in Selected Patients With Early Breast Cancer Trial International VErsion (PROSPECTIVE)

NCT06445738 | Recruiting DMC

• 1 other identifier: BCT 2401
• Study Type: interventional
• Target: 1,400
• Locations: 2 countries
• Sites: 9

Brief Summary

The PROSPECTIVE trial aims to find out if using the results of Magnetic Resonance Imaging (MRI) for early breast cancer can select people to not have radiotherapy and still have a low chance of the cancer coming back after surgery. The main question it aims to answer is: \* Will cancer come back in the same breast as the original cancer in patients who have surgery for their breast cancer, but who don't have radiotherapy afterwards because the results of an MRI before surgery showed favourable characteristics for not having radiotherapy.

Conditions

Breast Cancer; Breast Cancer Female

Keywords

Omission of radiotherapy; Magnetic Resonance Imaging (MRI)

Outcome Measures

Primary Outcomes (1)

• Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up

  To determine the ipsilateral invasive recurrence rate (IIRR) in lower risk patients with unequivocally unifocal breast cancer and on breast MRI and favourable clinico-pathological features.

  Median of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)

Secondary Outcomes (24)

• Ipsilateral Invasive Recurrence Rate (IIRR) in all participants omitting RT at a median of 10 years follow up after surgery.

  Median of 10 years follow up after surgery.

• IIRR in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.

  Median of 5 years and 10 years follow up after surgery.

• Ipsilateral DCIS recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.

  Median of 5 and 10 years follow up after surgery.

• The combined ipsilateral DCIS and invasive recurrence rate (IRR) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.

  Median of 5 and 10 years follow up after surgery.

• Regional recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.

  Median of 5 and 10 years follow up after surgery.

Other Outcomes (8)

• ET: Oncologic outcomes in relation to intensity of endocrine therapy (ET)

  Median of 5 and 10 years follow up

• Endocrine Therapy: Adherence to ET

  Measured at a median of 6-, 24- and 60- months follow-up post-surgery.

• Radiology: Outcomes of MRI

  At the time of the pre-operative MRI

Study Arms (2)

Radiotherapy Omission

EXPERIMENTAL

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")

Radiation: Arm A: Radiotherapy Omission

Standard Treatment

ACTIVE COMPARATOR

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.

Other: Arm B: Standard Treatment

Interventions

Arm B: Standard Treatment OTHER

Ineligible for RT omission on study; includes management of MRI-detected lesions.

Standard Treatment

Arm A: Radiotherapy Omission RADIATION

Omission of radiotherapy based on pre-surgical MRI and pathology findings at surgery.

Also known as: A1: Grade 1 or 2/HER2 negative; A2: Grade 3 and/or HER2 positive

Radiotherapy Omission

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written, informed consent to participate in the study.
• Female participants ≥ 50 years old with histologically\* confirmed ER-positive and/or HER2-positive invasive breast cancer.
• Has a life expectancy of at least 10 years and suitable for prolonged follow up for 10 years.
• Breast imaging indicating unifocal, unilateral breast cancer must have been performed before pre-registration.
• Willing/able to have surgery within 8 weeks of registration or pre-operative MRI, whichever occurs later.
• Have ECOG performance status 0-2.
• 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:
• 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+).
• + (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).
• + (HER2 positive): Circumferential membrane staining that is complete, intense and in \> 10% of tumour cells.

You may not qualify if:

• Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as ≥ 10% staining on IHC.
• Previous invasive breast cancer and/or DCIS in either breast.
• Prior RT to the breast or chest.
• Participants who plan to have a mastectomy for the index cancer.
• Lymphovascular invasion (LVI) reported on diagnostic core biopsy.
• Multifocal/multicentric breast cancer on breast imaging before registration.
• Distant metastasis at diagnosis.
• Bilateral breast cancer
• Known breast cancer predisposition gene mutation carriers (BRCA1, BRCA2, PALB2, CHEK2, ATM, CDK1, p53, BARD1, RAD51C, RAD51D, CDH1, STK11, PTEN).
• Contraindication to breast MRI scanning.
• Concurrent illness/conditions which limits life expectancy to 10 years or less.
• Has moderate or marked BPE in the breast containing the index cancer (where MRI is done before registration).
• Inability to give informed consent.
• Allocation: Arm A - Radiotherapy Omission
• Has nil/minimal or mild BPE in the breast containing the index lesion on pre-operative breast MRI.

Sponsors & Collaborators

• Breast Cancer Trials, Australia and New Zealand: lead

Study Sites (9)

UCSF Breast Care Center

San Francisco, California, 94158, United States

NOT YET RECRUITING

Baylor St Luke's Medical Centre

Houston, Texas, 77030, United States

NOT YET RECRUITING

The Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

NOT YET RECRUITING

Lake Macquarie Private Hospital

Gateshead, New South Wales, 2290, Australia

NOT YET RECRUITING

Mater Hospital, Sydney

North Sydney, New South Wales, 2060, Australia

RECRUITING

Westmead Hospital

Westmead, New South Wales, 2145, Australia

NOT YET RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

NOT YET RECRUITING

Monash Cancer Centre (MMC Moorabbin)

Clayton, Victoria, 3168, Australia

RECRUITING

The Royal Melbourne Hospital

Melbourne, Victoria, 3000, Australia

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Bruce Mann, MD

  Melbourne Health

  STUDY CHAIR

• Steven David, MD

  Peter MacCallum Cancer Centre - Moorrabin

  STUDY CHAIR

• Alastair Thompson, MD

  Baylor College of Medicine

  STUDY CHAIR

Central Study Contacts

Heath Badger

CONTACT

+61 2 4925 5239; heath.badger@bctrials.org.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A two-arm, non-randomised, prospective, multicentre study using MRI findings and pathology features to select patients with early breast cancer for omission of post-operative radiotherapy.

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: June 6, 2024
• Study Start: June 6, 2025
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): June 1, 2039
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will be made available for request after publication of the main/final study results; no end date.
• Access Criteria: 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).

Locations

AU (7); US (2)