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

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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.

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Study details:

Breast cancer is the most common serious malignancy in women and most patients are suitable for therapy involving surgery and adjuvant radiotherapy (RT). For most patients, there is a lack of evidence that breast conserving surgery without adjuvant RT is safe and therefore patients bear the costs, inconvenience and morbidity of RT. Prior attempts to identify large subsets of patients for whom RT can be safely omitted based on clinicopathological features of the index cancer have had limited success, and so RT is currently omitted only in some women over 65 or 70 with small low risk cancers.

Identification of a much larger subset of patients in whom adjuvant RT could be safely omitted would be hugely significant, not only to the patients, but to the entire health system. The ANZ 1002 PROSPECT study was a two-arm phase II study that used breast MRI findings and pathological features to identify a group of patients with low risk early breast cancer in whom RT may be safely omitted. The findings at the primary strongly support the hypothesis and suggest that the combination of preoperative MRI and pathological features can identify a substantial group of early breast cancer patients in whom adjuvant RT can be safely omitted.

A Health Economic analysis of PROSPECT found that the avoided costs of RT and its potential side effects is likely to substantially outweigh the extra cost of MRI scans and associated investigations. Parallel cross-sectional studies assessing Fear of Cancer Recurrence (FCR) and Health Related Quality of Life (HRQoL) in patients taking part in PROSPECT who either did or did not receive RT and a control group found a substantially lower FCR in PROSPECT patients who omitted RT as well as improved HRQoL. The majority of screened and eligible patients (427/443 and 193/201, respectively) for PROSPECT were recruited from two Australian sites.

Before the PROSPECT approach can be widely adopted, the findings need to be replicated in a multicentre, international study. In addition, patient reported outcomes and health economic assessments need to be performed prospectively and longitudinally. PROSPECTIVE is the follow-up to PROSPECT which will address these issues, and also include translational research aspects to further study the natural history and outcomes of this group of lower risk early breast cancers.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • 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.
  • 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.
  • 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.
  • Pathology material from index cancer must be available.
  • Have ECOG performance status 0-2.
  • Participants with Grade 3 cancer and/or HER2-positive cancer must agree to comply with systemic treatment recommendations.
  • Exclusion criteria

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

    Age eligible for study : 50 and older

    Healthy volunteers accepted : No

    Gender eligible for study: Female

    Things to know

    Study dates

    Study start: 2025-01-01

    Primary completion: 2032-01-01

    Study completion finish: 2039-01-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      NA

    trial

    Trial ID

    NCT06445738

    Intervention or treatment

    RADIATION: Arm A: Radiotherapy Omission

    OTHER: Arm B: Standard Treatment

    Conditions

    • Breast Cancer
    • Breast Cancer Female
    Image related to Breast Cancer
    • Condition: Breast Cancer, Breast Cancer Female

    • RADIATION: Arm A: Radiotherapy Omission and other drugs

    • Camperdown, New South Wales, Australia and more

    • Sponsor: Breast Cancer Trials, Australia and New Zealand

    Find a site

    Closest Location:

    The Chris O'Brien Lifehouse

    Research sites nearby

    Select from list below to view details:

    • The Chris O'Brien Lifehouse

      Camperdown, New South Wales, Australia

    • Lake Macquarie Private Hospital

      Gateshead, New South Wales, Australia

    • Westmead Hospital

      Westmead, New South Wales, Australia

    • Royal Adelaide Hospital

      Adelaide, South Australia, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/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")
    RADIATION: Arm A: Radiotherapy Omission
    • Omission of radiotherapy based on pre-surgical MRI and pathology findings at surgery.
    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.
    OTHER: Arm B: Standard Treatment
    • Ineligible for RT omission on study; includes management of MRI-detected lesions.

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow upTo determine the ipsilateral invasive recurrence rate (IIRR) in patients with favourable clinico-pathological features on MRI and unequivocally unifocal breast cancer treated with wide local excision but no adjuvant radiotherapyMedian of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)
    Ipsilateral Invasive Recurrence Rate (IIRR) in all patients omitting RT at a median of 5 years follow upTo determine the ipsilateral invasive recurrence rate (IIRR) in patients allocated to omit radiotherapyMedian of 5 years follow up

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Ipsilateral Invasive Recurrence Rate (IIRR) in all patients omitting RT at a median of 10 years follow upTo determine the ipsilateral invasive recurrence rate (IIRR) in patients allocated to omit radiotherapyMedian of 10 years follow up
    IIRR in higher risk patients omitting RT and the total cohort omitting RTTo determine the ipsilateral invasive recurrence rate (IIRR) in higher risk participants and the total cohort omitting RT.Median of 5 years follow up
    IIRR in the breast at 5 and 10 years in the entire cohort undergoing pre-operative MRI and ineligible for RT omissionTo determine the ipsilateral invasive recurrence rate (IIRR) in the breast at 5 and 10 years in the entire cohort undergoing preoperative MRI and found to be ineligible for RT omission after BCS (Arm B).Median of 5 and 10 years follow up.
    IIR in the breast at 5 and 10 years in the entire cohort undergoing pre-operative MRITo determine the ipsilateral invasive recurrence rate (IIRR) in the breast at 5 and 10 years in the entire cohort undergoing preoperative MRI (Arms A + B).Median of 5 and 10 years follow up
    Ipsilateral DCIS recurrence rate in the entire cohortTo determine the ipsilateral DCIS recurrence rate in the entire cohort undergoing pre-operative MRI (Arms A + B).Median of 5 and 10 years follow up.
    Ipsilateral DCIS and invasive recurrence rate in all cohorts separately and combinedIpsilateral DCIS and invasive recurrence rate in all cohorts separately and combinedMedian of 5 and 10 years follow up
    Regional recurrence rate in all participantsTo determine the regional recurrence rate in the entire cohort undergoing preoperative MRI (Arms A + B).Median of 5 and 10 years follow up
    Distant recurrence rate in all participantsTo determine the distant recurrence rate in the entire cohort undergoing preoperative MRI (Arms A + B).Median of 5 and 10 years follow up
    Contralateral DCIS and invasive breast cancer in each arm separately, and combinedTo determine the contralateral DCIS and invasive breast cancer in Arm A, Arm B, and the total cohort (Arms A + B)Median of 5 and 10 years follow up
    Breast cancer specific survival rate in all groups separately and combinedTo determine the breast cancer specific survival rate in all groups separately and combinedMedian of 5 and 10 years follow up
    Overall survival rateTo determine the overall survival rate in all groups separately and combinedMedian of 5 and 10 years follow up
    PRO: Fear of Cancer RecurrenceTo determine the difference in Fear of cancer recurrence (FCR) between Arm A and Arm B measured by the Fear of Cancer Recurrence Inventory Short Form (FCRI-SF). A higher score indicates a greater fear of recurrence.Median 24 months post-surgery
    PRO: HRQoL (functional and aesthetic outcomes)To determine the difference in HRQoL (functional and aesthetic outcomes) between Arm A and Arm B measured by the Breast Cancer Treatment Outcomes Scale (BCTOS). A higher score indicates greater morbidity.24 months post-surgery
    PRO: HRQoL (fatigue, body image, financial toxicity)To determine the difference in HRQoL (fatigue, body image, financial toxicity) between Arm A and Arm B measured by the EORTC ILXX measure (custom measure for this protocol). A higher score indicates greater fatigue, poorer body image and greater financial toxicity.24 months post-surgery
    PRO: Difference over time in FCRTo determine the difference over time in FCR between Arm A and Arm B measured by the FCRI-SF. A higher score indicates a greater fear of recurrence.From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery
    PRO: Difference over time in HRQoL (functional and aesthetic outcomes)To determine the difference over time in HRQoL (functional and aesthetic outcomes), between Arm A and Arm B measured by the BCTOS. A higher BCTOS score indicates greater morbidity.From allocation to 6-, 12-, 24- and 60 months median follow up post-surgery
    PRO: Difference over time in HRQoL (ffatigue, body image, financial toxicity)To determine the difference over time in HRQoL (fatigue, body image, financial toxicity), between Arm A and Arm B measured by the EORTC ILXX measure (custom measure for this protocol). A higher score indicates greater fatigue, poorer body image and greater financial toxicity.From allocation to 6-, 12-, 24- and 60 months median follow up post-surgery
    PRO: Differences in Quality of Life Years (QALYs)Differences in QALYs between Arm A and Arm B measured by the EQ-5D-5L24 months post-surgery

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

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    References

    Clinical Trials Gov: Post-operative Radiotherapy Omission in Selected Patients with Early Breast Cancer Trial International VErsion (PROSPECTIVE)

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