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…
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Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ipsilateral invasive breast cancer-free rate at 10 years.
The date of ipsilateral invasive breast cancer is the time of first appearance
of a suspicious lesion in any soft tissue of the ipsilateral breast (positive
cytology; a visible or palpable lesion), later proven to be a definite
ipsilateral invasive breast cancer (proven by positive histology).
Apart from ipsilateral invasive breast cancer, also regional, distant
metastases and death from breast cancer in the absence of ipsilateral invasive
breast cancer will be considered events. For more details see section 7.2.1.
Secondary outcome
* Rate of invasive disease assessed on the final pathology specimen (standard
arm only)
* Rate of grade III DCIS assessed on the final pathology specimen (standard arm
only)
* Biopsy rate for the ipsilateral breast during follow-up (both therapeutic
policies). Is defined as the rate of:
* Taking a re-biopsy of the index lesion in the active surveillance arm based
on the algorithm in chapter 5.3 or any clinically justified criteria
* Taking a biopsy of any new formed lesion at the site of in the place of the
pre-existing resected marked lesion or elsewhere in the ipsilateral breast
based on clinical and/or radiographic criteria (mammography, MRI, Ultrasound).
* Mastectomy rate for the ipsilateral breast (at baseline or for subsequent
ipsilateral DCIS or iBC) (both treatment arms)
* Time to ipsilateral DCIS of grade III (both therapeutic policies)
* Time to contralateral DCIS of grade I, II or III (both therapeutic policies)
* Time to contralateral invasive breast cancer (both therapeutic policies)
* Distant metastases free interval (both therapeutic policies)
* Overall survival (both therapeutic policies)
* Time to failure of active surveillance strategy (i.e. time to crossover to
standard treatment, due to any cause)
* Quality of life (both therapeutic policies)
* Cost-effectiveness (both therapeutic policies)
Background summary
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.
Study objective
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.
Intervention
Women in the experimental arm will not be treated for their low-risk DCIS.
They will be managed by an active surveillance strategy, i.e. monitoring by
annual digital mammography for a period of 10 years. If progression to
higher-grade DCIS or invasive cancer occurs, standard treatment for the present
indication will be given. A detailed schedule on how to detect possible
progression is provided in chapter 6.4 (follow-up).
Study burden and risks
In the "active surveillance'" group the patient will not receive the standard
treatment so the patient will not have to go to the hospital for a treatement
but we do ask patient to come to the hospital for the annual mammography. We
do not expect to be any side effects in this arm . While we think that the
active surveillance approach is equally safe as the standard treatment, there
is no proof of this yet so this might lead to psychological distress for the
patient.
In a minority of cases, low-risk DCIS can progress into invasive breast cancer.
However, this will be most probably low grade, oestrogen receptor positive
breast cancer with excellent outcomes without any adjuvant systemic treatment
(see www.adjuvantonline.com). Moreover, it is highly likely that those lesions
will be detected in a very early stage if active surveillance is applied.
Both groups will be asked to fill in questionnaires about Quality Of Life at 6
different timepoints.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent according to ICH/GCP, and national/local regulations
- Women >= 45 years old, any menopausal status
- Unilateral DCIS of any size
- American Society of Anesthesiologists (ASA) score 1 -2 and 3, only if able
to undergo surgery and yearly mammography (see Appendix E)
- Lesions of type 'calcifications only', detected by population-based or
opportunistic screening mammography
- Within twelve weeks of detection at least six 12 G biopsies (or the
equivalent of six 12 G needles) need to be taken from the area of the
calcification. This implies at least 7 cc volume irrespective of supplier, or
at least three 8G, four 9G, five 10G or five 11G biopsy needles need to be
taken to meet LORD*s eligibility criteria. Whatever needle size is applied, it
is essential to confirm that the biopsies contain representative calcifications
via biopsy radiography, microscopy, or both.
- In case of an extended lesion (> 5 cm): biopsies were taken from the center
and the periphery of the lesion, or from two peripheral parts of the lesion
- In case of multiple lesions with calcifications biopsies have been taken from
two, but not more, groups of calcifications
- Estrogen receptor >=80% positive and HER2 negative: 0 or 1+ or 2+ with
negative ISH), analysed centrally by pathology at NKI-AVL
- Marker placement at biopsy site (s) in the breast . Note: if patient prefers
surgery, marker placement is not mandatory.
- FFPE tissue blocks from the biopsy and, if applicable, from the resection
specimen, available for translational research purposes. If no FFPE tissue
blocks can be submitted, 10 unstained slides of 4-5 µm thickness from the
lesion(s) are acceptable
- Good correlation between pathological and radiological findings i.e. both
findings confirm low-risk DCIS and no suspicion high- grade DCIS or invasive
breast cancer
- The interval between histologic diagnosis of low-risk DCIS on biopsy and
randomization is <= 12 weeks
Exclusion criteria
-Estrogen receptor negative: <80% or HER2 positive: 3+, or 2+ with positive ISH
- Presence of either mass, increased focal density or architectural distortion
around the calcifications on mammography (suspicious for invasive disease)
- Presence of Paget*s disease, invasive breast cancer, or pleomorphic LCIS;
Lobular neoplasia, referring to atypical lobular hyperplasia (ALH) and/or
classic Lobular Carcinoma In Situ according to the WHO Classification of
Tumours of the Breast, is no reason to exclude
- Symptomatic DCIS e.g. DCIS detected by palpation or bloody nipple discharge
- Synchronous invasive carcinoma in the contralateral breast
- Prior history of invasive breast cancer or DCIS, prior surgery because of
benign breast lesion (s) is allowed
- Prior history of other cancer except carcinoma in situ of the cervix or basal
carcinoma of the skin
- Serious disease that precludes definitive surgical treatment (e.g
cardiovascular/ pulmonary/ renal disease)
- Individual with a family member with a known gene mutation associated with
increased risk of breast cancer, unless study participant is a proven
non-carrier of mutation
- Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule; those conditions should be discussed with the patient before
registration in the trial
- Pregnancy or breast-feeding. Contraceptive measures during the trial are
mandatory for those patients that will participate in standard treatment arm
and adequate counselling should be provided by the treating physician. The
duration of contraception will be specified by the treating physician according
to patient and treatment characteristics, standard clinical practice and
national regulations
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02492607 |
| CCMO | NL55612.031.16 |