EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer

NCT02889874 | Active Not Recruiting DMC

• 2 other identifiers: ANZ1601/BIG 16-022016-003527-33
• Study Type: interventional
• Target: 1,167
• Locations: 9 countries
• Sites: 68

Brief Summary

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.

Conditions

Early Stage Breast Carcinoma

Keywords

Radiation therapy; omission; non-inferiority; breast cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Local-regional recurrence-free interval (LRRFI)

  10 years

• Distant recurrence-free interval (DRFI)

  10 years

• Disease free survival including DCIS (DFS-DCIS)

  10 years

• Invasive disease free survival (iDFS)

  10 years

• Recurrence-free interval

  10 years

Other Outcomes (2)

• Quality of Life: Fear of recurrence

  5 years

• Quality of Life: Convenience of care

  5 years

Study Arms (2)

A: Radiation Therapy & endocrine therapy

NO INTERVENTION

Patients randomized to Arm A will receive standard radiation therapy and adjuvant endocrine therapy (standard of care).

B: No Radiation Therapy (ET only)

EXPERIMENTAL

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

Interventions

Omission of radiation therapy RADIATION

Omission of radiation therapy (adjuvant endocrine therapy only).

B: No Radiation Therapy (ET only)

Eligibility Criteria

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

You may qualify if:

• 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.
• For randomization to the study, patients must fulfill all of the following criteria:
• \. Primary tumour characteristics as assessed by Prosigna (PAM50) Assay:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Breast Cancer Trials, Australia and New Zealand: lead
• Breast International Group: collaborator
• ETOP IBCSG Partners Foundation: collaborator

Study Sites (68)

Sanatorio Britanico Rosariio

Rosario, Santa Fe Province, S2000, Argentina

Location

Instituto de Oncologia de Rosario

Santa Fe, Argentina

Location

Clinica Viedma

Sarmiento, R8500ACE, Argentina

Location

The Canberra Hospital

Canberra, Australian Capital Territory, 2605, Australia

Location

Macarthur Cancer Therapy Centre

Campbelltown, New South Wales, 2560, Australia

Location

The Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Hospital, Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Genesis Cancer Care Newcastle

Gateshead, New South Wales, 2290, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 1871, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Mater Hospital Sydney

North Sydney, New South Wales, 2060, Australia

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Tamworth Rural Referral Hospital

Tamworth, New South Wales, 2340, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Genesis Cancer Care Wesley

Auchenflower, Queensland, 4066, Australia

Location

Cancer Care Service - Bundaberg

Bundaberg, Queensland, 4670, Australia

Location

Cancer Care Service - Hervey Bay

Bundaberg, Queensland, 4670, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

GenesisCare Tennyson

Kurralta Park, South Australia, 5037, Australia

Location

Ballarat Austin Radiation Oncology Centre

Ballarat, Victoria, 3353, Australia

Location

Peter MacCallum Cancer Centre - Bendigo

Bendigo, Victoria, 3550, Australia

Location

Peter MacCallum Cancer Centre - Moorabin

Bentleigh East, Victoria, 3165, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Icon Cancer Centre Richmond

East Melbourne, Victoria, 3002, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

GenesisCare Radiation Oncology Centre Frankston

Frankston, Victoria, 3199, Australia

Location

University Hospital Geelong

Geelong, Victoria, 3220, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 8006, Australia

Location

Ringwood Radiation Oncology Centre

Ringwood East, Victoria, 3135, Australia

Location

Latrobe Regional Hospital

Traralgon, Victoria, 3844, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Hospital Luis Tisne Brousse

Santiago, Santiago Metropolitan, Chile

Location

Centro Oncologico del Norte

Antofagasta, Chile

Location

Hospital Sotero del Rio

Puente Alto, Chile

Location

Hospital Barros Luco Trudeau

San Miguel, Chile

Location

Instituto Nacional del Cancer

Santiago, 1010, Chile

Location

St Luke's Radiation Oncology Network

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

ASST Ospedale A. Manzoni UOS Oncologia

Lecco, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Palmerston North Hospital

Palmerston North, 4414, New Zealand

Location

Wellington Hospital

Wellington, 6021, New Zealand

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Arnoa de Vilanova de Lleida

Lleida, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hirslanden Clinique des Grangettes

Chêne-Bougeries, 1224, Switzerland

Location

Fondazione Oncologia Lago Maggiore

Locarno, 6600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8400, Switzerland

Location

Brust-Zentrum AG Zurich

Zurich, 8008, Switzerland

Location

Universitatsspital Zurich

Zurich, 8091, Switzerland

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407204, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Taipei Medical University Hospital

Taipei, Taiwan

Location

Chang-Gung Memorial Hospital

Taoyuan District, 10449, Taiwan

Location

Related Links

• Breast Cancer Trials (formerly Australia \& New Zealand Breast Cancer Trials Group

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Heath Badger

  Breast Cancer Trials, Australia and New Zealand

  STUDY DIRECTOR

• Boon H Chua, Prof

  Prince of Wales Hospital

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: August 25, 2016
• First Posted: September 7, 2016
• Study Start: August 21, 2017
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be made available for request after publication of the main/final study results; no end date.
• Access Criteria: Subject to approval by Breast Cancer Trials: contact concept@bctrials.org.au for further information. Note that there may be additional circumstances preventing BCT from sharing requested data as outlined in the BCT Data Sharing Guidelines .

Locations

ES (5); CL (5); CH (5); IT (2); NZ (4); AU (32); TW (10); AR (3); IE (2)