Save

EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer

RECRUITING

This is a randomised, phase III, non-inferiority trial evaluating radiation therapy versus observation following breast conserving surgery and planned endocrine therapy in patients with stage I breast cancer of luminal A subtype defined using the Prosigna (PAM50) Assay.

Simpliy with AI

Study details:

Radiation therapy (RT) after breast conserving surgery to improve local control and survival is the current standard of care for patients with early breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of RT in individual patients varies substantially. Thus, a pressing priority in contemporary breast cancer management is to tailor RT utilisation to the individual recurrence risks by identifying patients who are unlikely to benefit from RT, thereby avoiding the morbidity and costs of over-treatment.

It is recognised that selected patients with early breast cancer are unlikely to derive benefits from RT after breast conserving surgery. However, randomised trials have not consistently identified patients who may safely omit RT using conventional clinical-pathologic characteristics. Breast cancer intrinsic subtypes distinguished by gene expression profiling are shown to be associated with distinct clinical outcomes.

There is substantial evidence supporting the clinical validity of multigene assays including the PAM50-based Prosigna Assay that identifies intrinsic subtypes and generates a Risk of Recurrence score (ROR) to quantify individual risks of distant relapse. Multigene assays are increasingly integrated into clinical practice to inform chemotherapy decision, highlighting their substantial practice changing potential in personalising the use of RT for early breast cancer. A recent analysis of archived tumour specimens of 1,308 patients with early breast cancer has shown significant associations between local recurrence risk and the PAM50-defined intrinsic subtypes and ROR score.

EXPERT presents a unique opportunity of clinical and public health importance to optimise personalised local therapy for early breast cancer through precise, individualised quantification of local recurrence risk to identify low-risk patients for whom RT after breast conserving surgery may be safely omitted.

Simplify with AI

Eligibility criteria

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

Inclusion criteria

Female patients aged ≥ 50 years of any menopausal status.

Primary tumour characteristics as assessed by conventional histopathology: * Unifocal histologically confirmed invasive breast carcinoma * Maximum microscopic size ≤2 cm * Grade 1 or 2 histology * ER and PR positive in ≥10% of tumour cells in either the biopsy or breast conserving surgical specimen * HER2 negative on IHC (score 0 or 1+) or in situ hybridisation (ERBB2-amplification Ratio ERBB2/centromeres <2.0 or mean gene copy number <6). Equivocal IHC score (2+) must be assessed by ISH.

Primary tumour must be resected by breast conserving surgery with microscopically negative margins for invasive carcinoma and any associated ductal carcinoma in situ (no cancer cells adjacent to any inked edge/surface of specimen) or re-excision showing no residual disease.

Histologically confirmed negative nodal status determined by sentinel node biopsy or axillary dissection. Patients with pN0 (i+) disease are eligible for study participation (malignant cells ≤0.2 mm in regional lymph node(s) detected by hematoxylin-eosin (H&E) stain or IHC, including isolated tumour cells).

No evidence of distant metastasis.

Eligible for and willing to have adjuvant endocrine therapy.

ECOG performance status 0-2.

Availability of FFPE tumour block for Prosigna (PAM50) Assay.

Primary tumour characteristics as assessed by Prosigna (PAM50) Assay: * Luminal A intrinsic subtype * ROR score ≤60

Exclusion criteria

Primary tumour characteristics: * Presence of multifocal or multicentric invasive carcinoma or ductal carcinoma in situ; * Evidence of clinical or pathologic T4 disease (extension to the chest wall, oedema or ulceration of skin, satellite skin nodules, inflammatory carcinoma); * The invasive component of the primary tumour is present as micro-invasion only; * Grade 3 histology; * Presence of lymphovascular invasion

Contra-indication or unwillingness to have adjuvant endocrine therapy.

Planned to receive adjuvant chemotherapy or biologic therapy after breast cancer surgery, i.e. any systemic therapy other than endocrine therapy is not permitted. Any therapy unrelated to cancer is permitted at the discretion of investigators.

Treated with neoadjuvant endocrine therapy, chemotherapy or biologic therapy prior to breast cancer surgery.

Prior breast or thoracic RT for any condition.

Pre-operative breast imaging evidence of disease aside from the primary carcinoma resected by breast conserving surgery.

Concurrent invasive breast carcinoma or ductal carcinoma in situ (synchronous or metachronous).

Prior diagnosis of invasive breast carcinoma or ductal carcinoma in situ in either breast irrespective of disease free interval.

A diagnosis of non-breast malignancy <5 years prior to randomisation with the following exceptions: * Patients who are diagnosed with carcinoma in situ of cervix, endometrium or colon; melanoma in situ; and basal or squamous cell carcinoma of the skin at any time prior to randomisation are not excluded from study participation. * Patients who are diagnosed with other non-breast malignancy ≥5 years prior to randomisation and without evidence of disease recurrence are not excluded from study participation.

Significant comorbidity precluding definitive RT for breast cancer (e.g. cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus).

Life expectancy <10 years.

Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer.

Pregnant or lactating patients.

Inability to be registered to the study ≤8 weeks after the last surgical procedure for breast cancer.

Inability to commence RT (if randomised to receive RT) no later than 12 weeks from the last surgical procedure for breast cancer.

Inability to provide written informed consent.

Psychiatric, addictive, or any disorder that precludes compliance with protocol requirements.

Simplify with AI

Eligibility

Age eligible for study : 50 and older

Healthy volunteers accepted : No

Gender eligible for study: Female

Things to know

Study dates

Study start: 2017-08-21

Primary completion: 2025-10-01

Study completion finish: 2026-04-01

Study type

TREATMENT

Phase

Trial ID

NCT02889874

Intervention or treatment

RADIATION: Omission of radiation therapy

Conditions

• Early Stage Breast Carcinoma

Image related to Early Stage Breast Carcinoma

Condition: Early Stage Breast Carcinoma
RADIATION: Omission of radiation therapy
Darlinghurst, New South Wales, Australia and more
Sponsor: Breast Cancer Trials, Australia and New Zealand

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

St Vincent's Hospital, Sydney

Research sites nearby

Select from list below to view details:

St Vincent's Hospital, Sydney
Darlinghurst, New South Wales, Australia
Gosford Hospital
Gosford, New South Wales, Australia
Calvary Mater Newcastle
Newcastle, New South Wales, Australia
Port Macquarie Base Hospital
Port Macquarie, New South Wales, Australia

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/Arm	Intervention/Treatment
NO_INTERVENTION: A: Radiation Therapy & endocrine therapy Patients randomized to Arm A will receive standard radiation therapy and adjuvant endocrine therapy (standard of care).	Not specified
EXPERIMENTAL: B: No Radiation Therapy (ET only) Patients randomized to Arm B will not receive radiation therapy (omission of radiation therapy) and receive adjuvant endocrine therapy only.	RADIATION: Omission of radiation therapy Omission of radiation therapy (adjuvant endocrine therapy only).

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Local recurrence rate after breast conserving surgery	The time from randomisation to the date of local recurrence (LR) as a site of first recurrence.	10 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Local-regional recurrence-free interval (LRRFI)	Time from randomisation to the date of local or regional recurrence as a site of first recurrence.	10 years
Distant recurrence-free interval (DRFI)	Time from randomisation to the date of distant recurrence, regardless of occurrence of any intervening local or regional recurrence, contralateral breast cancer or second (non-breast) primary invasive cancer.	10 years
Disease free survival including DCIS (DFS-DCIS)	Time from randomisation to date of first evidence of local (invasive breast carcinoma or DCIS), regional or distanct recurrence; contralateral breast cancer (invasive breast carcinoma or DCIS); second (non-breast) primary invasive cancer; or death.	10 years
Invasive disease free survival (iDFS)	Time from randomisation to date of first evidence of local (invasive breast carcinoma), regional or distanct recurrence; contralateral breast cancer (invasive breast carcinoma); second (non-breast) primary invasive cancer; or death.	10 years
Recurrence-free interval	Time from randomisation to the date of local, regional or distant recurrence as a site of first recurrence.	10 years
Overall survival (OS)	Time from randomisation to date of death from any cause.	10 years
Salvage RT or mastectomy rate	Time from randomisation to the receipt of salvage RT or mastectomy, individually and in combination (one or the other) as a composite endpoint.	10 years
Adverse events for patients	Adverse events during treatment (up to 5 years of endocrine therapy) assessed using NCI CTCAE v4.0.	5 years
Assessment of the impact of endocrine therapy	FACT-ES measure of endocrine symptoms.	5 years

Frequently Asked Questions

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

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

Clinical Trials Gov: EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer