Management of Low-risk (Grade I and II) DCIS

Not Applicable

Recruiting

• Conditions: DCIS
• Interventions: Other: Standard treatment; Device: digital mammography; Radiation: radiotherapy

• Registration Number: NCT02492607
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns slow-growing low-risk DCIS (grade I and II). This implies that many women might be unnecessarily going through intensive treatment resulting in a decrease in quality of life and an increase in health care costs, without any survival benefit.

The LORD (LOw Risk DCIS) study is a non-randomized, international, multicenter, phase III non-inferiority trial, and aims to determine whether screen-detected low-risk DCIS can safely be managed by an active surveillance strategy or that the conventional treatment, being either WLE alone, WLE + RT, or mastectomy, and possibly HT, should remain the standard of care.

Detailed Description

Background of the study:

The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists. We hypothesize that asymptomatic, low-risk DCIS (grade I and II DCIS) can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be lowgrade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. It also may save many low-risk DCIS patients from intensive treatment.

Objective of the study:

The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years.

Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate and patient reported outcomes. To determine whether low- risk DCIS can safely (measured by ipsilateral invasive breast cancer rate at 10 years) be managed by an active surveillance strategy or if the conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy, will remain the standard of care.

Study design:

Phase III, open-label, non-inferiority, multi-center, non-randomized clinical trial. By patient's preference, women will be included into one of the following arms: active surveillance or standard treatment according to local policy, being either WLE alone, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of five years and an additional two mammograms at year seven and ten.

Study Timeline

• Study First Submitted: 2015-06-24
• Study First Submitted QC: 2015-07-07
• Study First Posted: 2015-07-08
• Study Start: 2017-02-13
• Status Verified: 2023-09
• Last Update Submitted: 2024-04-03
• Last Update Posted: 2024-04-05
• Primary Completion: 2034-02-01
• Study Completion: 2034-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 2500

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard treatment	radiotherapy	Standard treatment according to local policy. This can be either wide local excision only, wide local excision and radiotherapy, or mastectomy. Hormonal therapy is also allowed. Follow-up:by annual digital mammography for a period of 5 years and a digital mammography at 7 and 10 years.
Standard treatment	Standard treatment	Standard treatment according to local policy. This can be either wide local excision only, wide local excision and radiotherapy, or mastectomy. Hormonal therapy is also allowed. Follow-up:by annual digital mammography for a period of 5 years and a digital mammography at 7 and 10 years.
Active surveillance	digital mammography	Active surveillance : monitoring by annual digital mammography for a period of 5 years and a digital mammography at 7 and 10 years.

Primary Outcome Measures

Name	Time	Method
Ipsilateral invasive breast cancer-free rate at 10 years	10 years from inclusion	Ipsilateral invasive breast cancer-free rate at 10 years (both therapeutic policies

Secondary Outcome Measures

Name	Time	Method
Biopsy rate for ipsilateral breast during follow-up	from inclusion to the time of death, during 10 years at minimum	Biopsy rate for ipsilateral breast during follow-up (both therapeutic policies)
Time to ipsilateral grade III DCIS	from inclusion to the development of a new ipsilateral DCIS of grade III, up to 10 years	Time to ipsilateral grade III DCIS, both therapeutic policies
Time to failure of active surveillance strategy	from inclusion to the time patients received standard treatment to the ipsilateral breast, up to 10 years	Time to failure of active surveillance strategy, i.e. time to crossover to standard treatment, due to any cause
Distant metastases free interval	from inclusion to the time of invasive distant metastases or death due to breast cancer, up to 10 years	Distant metastases free interval,both therapeutic policies
Rate of invasive disease at the final pathology specimen (standard arm only)	from inclusion till time of invasive disease during 10 years at minimum	Rate of invasive disease at the final pathology specimen (standard arm only)
Rate of grade III DCIS at the final pathology specimen (standard arm only)	from inclusion till time of invasive disease during 10 years at minimum	Rate of grade III DCIS at the final pathology specimen (standard arm only)
Time to contralateral DCIS	from inclusion to the development of a new contralateral DCIS I,II,III, up to 10 years	Time to contralateral DCIS, both therapeutic policies
Cost-effectiveness	6 times from inclusion to 10 years follow-up	Health economic evaluation (both therapeutic policies)
Health Related Quality of life	6 times from inclusion to 10 yrs follow-up	General QoL/global health perception, specific funcionalities, pain ( both therapeutic policies
Overall survival	from inclusion to the time of death, during 10 years at minimum	Overall survival,both therapeutic policies
Masectomy rate for ipsilateral breast	from inclusion to the time of ipsilateral breast cancer or death, during 10 years at minimum	Masectomy rate for ipsilateral breast, baseline or subsequent ipsilateral DCIS or iBC (both therapeutic policies)
Time to contralateral invasive breast cancer	from inclusion to the development of a contralateral invasive breast cancer, up to 10 years	Time to contralateral invasive breast cancer,, both therapeutic policies

Trial Locations

Locations (59)

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands

Maxima Medisch Centrum; 🇳🇱 Eindhoven, Netherlands

Haga ziekenhuis loc Zoetermeer; 🇳🇱 Zoetermeer, Netherlands

Gelre ziekenhuizen; 🇳🇱 Zutphen, Netherlands

Noordwest Ziekenhuisgroep- site Alkmaar; 🇳🇱 Alkmaar, Netherlands

Onze Lieve Vrouwe Gasthuis; 🇳🇱 Amsterdam, Netherlands

Rode Kruis Ziekenhuis; 🇳🇱 Beverwijk, Netherlands

Alexander Monro Ziekenhuis; 🇳🇱 Bilthoven, Netherlands

Amphia Ziekenhuis; 🇳🇱 Breda, Netherlands

Canisius-Wilhelmina Ziekenhuis; 🇳🇱 Nijmegen, Netherlands

Flevoziekenhuis; 🇳🇱 Almere, Netherlands

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis; 🇳🇱 Amsterdam, Netherlands

Wilhelmina Ziekenhuis Assen; 🇳🇱 Assen, Netherlands

Rijnstate Ziekenhuis; 🇳🇱 Arnhem, Netherlands

Deventer Ziekenhuis; 🇳🇱 Deventer, Netherlands

Reinier de Graaf Gasthuis; 🇳🇱 Delft, Netherlands

HagaZiekenhuis; 🇳🇱 Den Haag, Netherlands

Slingeland Ziekenhuis; 🇳🇱 Doetinchem, Netherlands

Albert Schweitzer Ziekenhuis; 🇳🇱 Dordrecht, Netherlands

Ziekenhuis Gelderse Vallei; 🇳🇱 Ede, Netherlands

Medisch Spectrum Twente Ariensplain; 🇳🇱 Enschede, Netherlands

Martini Ziekenhuis; 🇳🇱 Groningen, Netherlands

Groene Hart Ziekenhuis; 🇳🇱 Gouda, Netherlands

Universitair Medisch Centrum Groningen; 🇳🇱 Groningen, Netherlands

Spaarne Gasthuis; 🇳🇱 Haarlem, Netherlands

Saxenburgh Medisch Centrum; 🇳🇱 Hardenberg, Netherlands

Ziekenhuis St. Jansdal; 🇳🇱 Harderwijk, Netherlands

Tjongerschans Ziekenhuis; 🇳🇱 Heerenveen, Netherlands

Zuyderland Medisch Centrum; 🇳🇱 Heerlen, Netherlands

Ziekenhuisgroep Twente; 🇳🇱 Hengelo, Netherlands

Jeroen Bosch Ziekenhuis; 🇳🇱 Hertogenbosch, Netherlands

Spaarne ziekenhuis; 🇳🇱 Hoofddorp, Netherlands

Treant Zorggroep Bethesda; 🇳🇱 Hoogeveen, Netherlands

Ter Gooi; 🇳🇱 Hilversum, Netherlands

Dijklander; 🇳🇱 Purmerend, Netherlands

Medisch Centrum Leeuwarden; 🇳🇱 Leeuwarden, Netherlands

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Netherlands

Alrijne Ziekenhuis; 🇳🇱 Leiderdorp, Netherlands

Haaglanden MC Antoniushove; 🇳🇱 Leidschendam, Netherlands

Academisch Ziekenhuis Maastricht; 🇳🇱 Maastricht, Netherlands

St. Antonius Ziekenhuis; 🇳🇱 Nieuwegein, Netherlands

Erasmus Medisch Centrum; 🇳🇱 Rotterdam, Netherlands

Maasstad Ziekenhuis; 🇳🇱 Rotterdam, Netherlands

Franciscus Gasthuis en Vlietland; 🇳🇱 Schiedam, Netherlands

Zuyderland Ziekenhuis; 🇳🇱 Sittard, Netherlands

Antonius Ziekenhuis; 🇳🇱 Sneek, Netherlands

Zorgsaam Zeeuws-Vlaanderen; 🇳🇱 Terneuzen, Netherlands

Zorgsaam Ziekenhuis; 🇳🇱 Terneuzen, Netherlands

St. Elisabeth Ziekenhuis; 🇳🇱 Tilburg, Netherlands

Ziekenhuis Rivierenland; 🇳🇱 Tiel, Netherlands

Bernhoven Ziekenhuis; 🇳🇱 Uden, Netherlands

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

Diakonessenhuis; 🇳🇱 Utrecht, Netherlands

Maxima Medisch Centrum - Locatie Veldhoven; 🇳🇱 Veldhoven, Netherlands

St Jans Gasthuis; 🇳🇱 Weert, Netherlands

VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo; 🇳🇱 Venlo, Netherlands

Streekziekenhuis Koningin Beatrix; 🇳🇱 Winterswijk, Netherlands

Zaans Medisch Centrum; 🇳🇱 Zaandam, Netherlands

Isala Klinieken; 🇳🇱 Zwolle, Netherlands