Primary objective: To determine whether there is an overall survival benefit for patients with an intermediate risk breast cancer from chest wall irradiation following mastectomy, in addition to treatment with optimal modern systemic therapy.…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is overall survival
Secondary outcome
Evaluation of the effects of chest wall irradiation on: chest wall recurrences,
regional recurrrences, disease free survival, metastasis free survival,
cause-specific survival (breast cancer, cardiac and non-cardiac), and early and
late morbidity. Molecular radiobiological differences between patients with or
without a local recurrence.
Background summary
Loco-regional radiotherapy following mastectomy for breast cancer is standaard
treatment for patients with high risk tumours (stage T3 and/ or N2 disease with
more than 3 lymph node metastases). Analysis of trials of postmastectomy
radiotherapy (PMRT) and overviews of these trials suggests that there is also a
clinically significant survival advantage from PMRT for patients with
intermediate risk disease (stages T1N1-T2N1) with a 17% reduction in the odds
of death and an absolute survival advantage of 9% - 7% after 14 and 20 years
respectively (Danish and Canadian trials). Because most locoregional
recurrences occur on the chest wall, most of the survival advantage is thought
(but not proven) to be due to the chest wall irradiation, rather than the nodal
irradiation.
Study objective
Primary objective: To determine whether there is an overall survival benefit
for patients with an intermediate risk breast cancer from chest wall
irradiation following mastectomy, in addition to treatment with optimal modern
systemic therapy.
Secondary objective: evaluation of the effects of chest wall irradiation on:
chest wall recurrences, regional recurrences, disease free survival, metastasis
free survival, cause-specific survival, and early and late morbidity. Futher to
carry out translational research with tumour and blood material to identify
molecular biological factors that are related for example to local recurrence
risk and radiation resistance (TRANS-SUPREMO substudy)
Study design
A phase III randomised trial with randomisation between chest wall irradiation
following mastectomy (and, if indicated, chemotherapy), versus no chest wall
irradiation.
Intervention
One randomisation group recieves chest wall irradiation, 40-50 Gy in 15-25
fractions over 3-5 weeks, and the controle group does not have radiotherapy.
Study burden and risks
Patients taking part in the TRANS-SUPREMO substudy (translational research)
will be asked to give 30 ml of blood. For patients taking part in the main
trial, with randomisation to no chest wall irradiation (the control group),
there is no additional burden. For patients in the intervention group with
chest wall irradiation, there is the following additional burden: before the
start of the irradiation simulation of the treatment set-up with a simulator of
CT scan (15-30 minutes) and marks are made on the skin. The radiation is given
in 15-25 sessions during 3-5 weeks. The time per session is 10-15 minutes, plus
travelling time to the hospital. Weekly on treatment check-ups by the
radiotherapist (external physical examination). Side effects of the radiation
are: skin redening with an itchy burning sensation, this goes away after the
end of the treatment. Late side effects are: a tight feeling in the skin of the
chest wall (fibrosis), radiation pneumonitis (1%), ribfractures (1-2%) and
possible heart problems at 10 years or more. After the radiotherapy there is
standard clinical follow-up, as for the control group.
This study is justified because with this trial we want to obtain a survival
advantage of chest wall irradiation for breast cancer patients. The risks of
chest wall irradiation are generally limited and not life-threatening.
Avenue E. Mounier 83/11
Brussel 1200
BE
Avenue E. Mounier 83/11
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
1. 1 Stage II histologically confirmed unilateral breast cancer following
mastectomy including the following pTNM stages:
-pT1, pN1, M0
-pT2, pN1, M0
-pT2, pN0 if grade III histology and/or lymphovascular invasion.
-pT3N0M0
If the tumour area comprises multiple small adjacent foci of invasive carcinoma
then overall maximum dimension taken to determine the T staging. Multifocal or
multicentric tumours can be included. The size of the largest tumour determines
the T stage classification.
1.2 Stage II histologically confirmed unilateral breast cancer following
neoadjuvant systemic therapy and mastectomy, if the original clinical stage was
cT1-2cN0-1 or cT1-2pN1(sn)M0 and with the following (ypTNM) stages after
neoadjuvant systemic therapy:
- ypT1N1M0
- ypT2pN1M0
- ypT2pN0M0 if grade III histology and/or lyphovascular invasion
- ypT0pN0 or ypT1pN0 or ypT0pN1 9pathological complete remission or near
complete remission)
-ypT2N0, independant of grade or lymphovascular invasion, if the priginal stage
was cT3N0
also:
-ypT3N0M0, if the original clinical staging was cT1-3cN0M0 or cT1-3pN0 (sn) M0,
1.3 Unilateral invasive breast cancer that conforms to the initial clinical
staging of criterion 1, but has been downstaged by neoadjuvant systemic therapy
to ypT0N0 or ypT1pN0 or ypT0N1 (pathological complete remission or near
complete remission). If the tumour stage cT3 or ypT3, then nodal status must be
N0 both before ans after neoadjuvant systemic therapy., 2. Undergone total
mastectomy (with minimum of 1 mm clear margin of invasive cancer and DCIS) and
axillary staging procedure., 3.1 If axillarynode positive (1-3 positive
nodes[including micrometastases >0.2 mm->= 2mm]) then an axillary node
clearance (minimum 8 nodes removed) should have been performed. Isolated tumour
cells do not count as micrometastases., 3.2 Axillary node status can be
determined on the basis of either axillary clearance or axillary node sampling
or sentinel node biopsy., 3.3 Sentinel nodes identified in the internal mammary
chain are considered pN1b or pN1c if histologically proven. Patients can be
included in the trial with microscopic metastasis in the internal mammary chain
detected by sentinel node biopsy, if not more than 3 tumour positive nodes in
axillaey lymph nodes. If not biopsied, internal mammary chain sentinel nodes
are considered tumour negative for staging., 3.5 Before neoadjuvant systemic
therapy, axillary ultrasound is advised. Abnormal axillary nodes based on
imaging (mammogram or ultrasound) should be sampled by guided needle sampling
or core biopsy. Where axillary ultrasound is normal, negative axillary node
status does not require histological confirmation before starting neoadjuvant
systemic therapy. Positive, or negative, nodal status may also be determined by
sentinel node biopsy before start of neoadjuvant therapy.
4. Fit for adjuvant chemotherapy (if indicated), adjuvant endocrine therapy (if
indicated) and postoperative irradiation.
axillary node sampling or sentinel node biopsy.
5. Written, informed consent.
NB Patients undergoing immediate breast reconstruction are eligible for
inclusion.
Exclusion criteria
1. Any pT0pN0-1,or pT1pN0 tumours after primary surgery.
2. Any pT3pN1 or pT4 tumours. Initial stage cT3cN1 or pN1(sn) or cT4 in
patients receiving neoadjuvant systemic therapy cannot be included, even if
downstaging has occured and the pathological ypT and N stage is lower.
3. Patients who have 4 or more pathologically involved axillary nodes. For the
purpose of this study protocol, nodal scaring after neoadjuvant systemic
therapy will be considered as evidence of previous pathological nodal
involvement and count towards the total number of involved axillary nodes.
4. Past history or current diagnosis of ductal carcinoma in situ (DCIS) of the
contralateral breast, unless treated by mastectomy. Previous DCIS of the
ipsilateral breast if treated with radiotherapy (i.e. previous DCIS treated by
conservation surgery not followed by radiotherapy would be considered eligible.)
5. Bilateral breast cancer. However, patients who have undergone a prophylactic
contralateral mastectomy can be included, if the breast was pathologically free
of invasive tumour.
6. Previous or concurrent malignancy other than non melanomatous skin cancer
and carcinoma in situ of the cervix. For previous DCIS see criterion 4., 7.
Male , 8. Pregnancy, at the time of radiotherapy treatment., 9. Not fit for
surgery, radiotherapy or adjuvant systemic therapy, 10. Unwilling or unable to
give informed consent.
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 |
|---|---|
| CCMO | NL13909.031.06 |