|- candidate number||5826|
|- NTR Number||NTR1797|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-mei-2009|
|- Secondary IDs||NL23017.031.08 NKI-AVL|
|- Public Title||Onderzoek naar het bepalen van de reactie op chemotherapie van tumorcellen in de borst en in de oksel.|
|- Scientific Title||Tumorresponse monitoring in patients with breast cancer treated with primary systemic therapy: Towards predicting response in both the primary tumor and in axillary lymph nodes.|
|- hypothesis||The aim of this protocol is twofold.|
1. Firstly, we aim to combine the new response monitoring method (PET imaging) with the present technique (dynamic CE-MRI imaging) in order to discriminate between favourable and unfavourable response of the primary tumor during and after neoadjuvant chemotherapy;
2. Secondly, we aim to investigate whether the axillary tumor response to primary systemic therapy can be reliably assessed.
|- Healt Condition(s) or Problem(s) studied||Breast cancer, Axillary lymph node metastasis|
|- Inclusion criteria||1. Proven infiltrating breast cancer with either a primary tumor over 3 cm in size (clinical examination) or cytologically proven spread to the axillary lymph nodes;|
2. Stage II or stage III disease (revised AJCC staging system 2001). 'Locally advanced breast cancer' patients are consequently eligible, including those with ipsilateral supraclavicular lymph node metastases. In stage II patients with T1N1 disease, N1 status must have been demonstrated by either fine needle aspiration from an axillary lymph node or by a metastasis of over 2 mm in diameter at sentinel node biopsy. Stage IIA patients are only eligible if the tumor is over 3 cms in diameter;
3. Age 18 to 65 years; patients older than 65 years may be included when considered 'biologically 65 years or younger';
4. Performance status: WHO 0 or I;
5. Adequate bone marrow function (W.B.C. count > 3.0 x 109/l, platelets > 100 x 109/l);
6. Adequate hepatic function (ALAT, ASAT and bilirubin < 2 x upper limit of normal);
7. Adequate renal function (creatinine clearance > 60 ml/min);
8. Radionuclide ejection fraction > 0.509;
9. Informed consent.
|- Exclusion criteria||1. Evidence of distant metastases. Staging examinations must have included a chest roentgenogram, an ultrasound examination of the liver and an isotope bone scan. Abnormal uptake on the isotope bone scan can only be accepted if bone metastases were excluded by MRI;|
2.Previous radiation therapy or chemotherapy;
3. Other malignancy except carcinoma in situ, unless the other malignancy was treated 5 or more years ago with curative intent without the use of chemotherapy or radiation therapy;
4. Pregnancy or breast feeding must be excluded and patients must use adequate contraceptive protection.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-jul-2008|
|- planned closingdate||1-jul-2012|
|- Target number of participants||300|
|- Interventions||1. 3x FDG-PET/CT (before and early during the chemotherapy course);|
2. Iodine-125 seeds localisation of proven lymph node metastases before neoadjuvant chemotherapy;
3. Selectively removal of marked nodes after neoadjuvant chemotherapy.
|- Primary outcome||Sensitivity and specificity of FDG PET and MRI to predict a favourable tumour response of the primary tumor defined as (near) pathological complete remission
Sensitivity and specificity of FDG PET/CT and radioactive I-125 seed localisation to predict a favourable tumour response of the axilla, defined as pathological complete remission or residual micrometastasis.|
|- Secondary outcome||Fusion of PET images with MRI images to achieve better anatomical localisation and to compare tumour response evaluation.|
|- Timepoints||3x FDG-PET/CT (before and early during the chemotherapy course)
Iodine-125 seeds localisation of proven lymph node metastases before neoadjuvant chemotherapy and selectively removal of marked nodes after neoadjuvant chemotherapy.|
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Drs. M. Straver|
|- CONTACT for SCIENTIFIC QUERIES||Dr. M.T.F.D. Vrancken Peeters|
|- Sponsor/Initiator ||Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI AVL) |
(Source(s) of Monetary or Material Support)
|- Brief summary||1. Response monitoring of the primary tumor:|
We will weigh the value of FDG-PET imaging against dynamic contrast-enhanced MRI to evaluate response of the primary tumor. It is expected that these modalities will complement one another in two ways:
A. MRI provides information on perfusion, whereas FDG provides tumor information on cell metabolism;
B. FDG PET may provide earlier assessment of tumor response than MRI for subgroups of patients.
In order to establish the optimal time point for FDG PET we will perform the PET early after initiating treatment and together with MRI at a later stage during treatment. The PET will be performed in prone orientation of the patient using a support system identical to the breast coil used at MRI. MRI and PET will be registered. Changes in the maximum standardized uptake
value (SUV) in the tumor and changes in size will be established at PET. At MRI changes in size of initial contrast uptake, and washout will be established. Presence/absence of residual disease at histopathology will be used as a surrogate end-point of tumor response. A favorable response is defined as a pathological complete remission (pCR); no residual tumor cells seen at microscopy, or a near pCR; a small number of scattered tumor cells. Multivariate analysis of changes in FDG uptake and MRI contrast uptake will be employed to establish quantitative guidelines to discriminate between favourable and non-favourable responders during neoadjuvant therapy. The guidelines will be constructed in a training set of cases and prospectively applied in a validation set of cases.
2. Response monitoring of the axilla:
In the group of cN1 patients, axillary tumor response will be evaluated using two different methods.
A. FDG-PET/CT. Patients will receive three FDG-PET/CT. One scan prior to primary systemic therapy, two PET scans during systemic therapy. ALND will be performed in all patients. The axillary tumor response as seen on FDG-PET will be compared with pathological assessment of the lymph nodes after ALND;
B. Radioactive seed localization (RSL). The tumor positive axillary lymph node will be marked prior to primary systemic therapy. In the same session of surgery for the breast tumor after systemic therapy, the marked lymph node will be detected using a gamma-ray detection probe (NEO 2000, Johnson and Johnson) and selectively removed. After removal of the marked lymph node, an ALND will be performed. The correlation between the tumor response in the marked lymph node and tumor response in the ALND specimen will be investigated.
During this study all patients will receive an ALND and a model will be generalized to predict an axillary favorable response, which is defined as as pathological complete remission or residual micrometastasis (< 2mm). In a future study, patients with a favourable response will be treated with axillary radiation therapy instead of axillary lymph node dissection.
|- Main changes (audit trail)|
|- RECORD||25-mei-2009 - 23-sep-2009|