Raw JSON Patch
[
{
"op": "replace",
"path": "/protocolSection/statusModule/statusVerifiedDate",
"value": "2019-07"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/startDateStruct/date",
"value": "2019-06-15"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/startDateStruct/type",
"value": "ACTUAL"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/primaryCompletionDateStruct/date",
"value": "2021-01"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/completionDateStruct/date",
"value": "2025-08"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdateSubmitDate",
"value": "2019-07-22"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"value": "2019-07-23"
},
{
"op": "remove",
"path": "/protocolSection/oversightModule/isUsExport"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/interventions/1/description",
"value": "Dose dense AC-T chemotherapy: consisting of 4 cycles of AC (doxorubicin and cyclophosphamide at a dose of 60 and 600 mg/m² as an i.v.\nbolus, respectively) 2-weekly, plus G-CSF (6 mg once per cycle) 24-48 hr after chemotherapy, followed by cycles of T (4 cycles docetaxel 100 mg/m² 3-weekly or 12 cycles paclitaxel 80 mg/m2 weekly)."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
"value": "Determine if ribociclib plus letrozole gives a ≥100% improvement in CCCA as compared to chemotherapy in the surgical specimen."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"value": "Correlation of tumor measurements between standard MRI (using RECIST 1.1) and palpation (largest diameter in cm) at baseline, after AC/before T or 8 weeks of definitive neoadjuvant therapy and pre-surgery."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"value": "Tumor measurements (MRI and palpation) will be performed at baseline, after AC/before T or 8 weeks of definitive neoadjuvant therapy and pre-surgery (which is around 7 months after start of initial letrozole treatment)."
},
{
"op": "replace",
"path": "/protocolSection/eligibilityModule/eligibilityCriteria",
"value": "<p>Inclusion Criteria:</p><ul><li>Postmenopausal women presenting with histological proven (core biopsy material) hormone receptor positive (ER≥50%, PR any), HER2 negative, stage II/ III breast cancer.</li><li>Measurable disease (breast and/or lymph nodes)</li><li>WHO 0-2</li><li>Adequate bone marrow function (within 4 weeks prior to registration): WBC≥3.0x109/l,\nneutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l</li><li>Adequate liver function (within 4 weeks prior to registration): bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL</li><li>Adequate renal function (within 4 weeks prior to registration): the calculated creatinine clearance should be ≥50 ml/min</li><li>Accessible for treatment and follow-up</li><li>Written informed consent</li></ul><p>Inclusion criteria randomization specific:</p><p>In order to be eligible to be randomized in this study, a subject must meet all of the following criteria:</p><ul><li>Registration in the NEOLBC trial before 2 weeks biopsy</li><li>Use of letrozole</li><li>Outcome central Ki67 determination in two weeks biopsy available.</li></ul><p>Exclusion Criteria:</p><ul><li>Evidence of distant metastases (M1)</li><li>Previous invasive breast cancer</li><li>Prior chemotherapy, radiation therapy or hormonal therapy with the exception of patients who received letrozole ≤ 14 days (+ max. 4 days) prior to registration and who are still on letrozole.</li><li>Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.</li><li>Peripheral neuropathy > grade 2, whatever the cause</li><li>Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias or on screening, any of the following cardiac parameters: bradycardia (heart rate <50 at rest) or QTcF ≥450 msec.</li><li>Known hypersensitivity reaction to any of the components of the treatment (peanuts, soy)</li><li>Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise.\nTherapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.</li><li><p>Currently receiving any of the following substances and cannot be discontinued 7 days prior to randomisation:</p><ul><li>Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelo's, star-fruit, pomegranate and Seville oranges.</li><li>That have a known risk to prolong the QT interval or induce Torsades de Pointes.</li><li>That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.</li><li>Herbal preparations/medications, dietary supplements.</li></ul></li><li>Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.</li></ul>"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/centralContacts/1/phone",
"value": "+31715299126"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/1/facility",
"value": "Ziekenhuisgroep Twente"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/3/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/4/facility",
"value": "Onze Lieve Vrouwe Gasthuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/4/contacts/0/name",
"value": "E. Kerver"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/facility",
"value": "Gelre Ziekenhuizen"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/city",
"value": "Apeldoorn"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/contacts/0/name",
"value": "S. Tromp - van Driel"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/geoPoint/lat",
"value": 52.21
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/5/geoPoint/lon",
"value": 5.96944
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/facility",
"value": "Amphia Ziekenhuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/city",
"value": "Breda"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/contacts/0/name",
"value": "J. Heijns"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/geoPoint/lat",
"value": 51.58656
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/6/geoPoint/lon",
"value": 4.77596
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/7",
"value": {
"city": "Delft",
"status": "NOT_YET_RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "M. van Bekkum",
"role": "CONTACT"
}
],
"facility": "Stichting Reinier Haga Groep (Reinier de Graaf Gasthuis)",
"geoPoint": {
"lat": 52.00667,
"lon": 4.35556
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/8",
"value": {
"city": "Deventer",
"status": "RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "L. Kessels",
"role": "CONTACT"
}
],
"facility": "Stichting Deventer Ziekenhuisgroep",
"geoPoint": {
"lat": 52.255,
"lon": 6.16389
}
}
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/10/facility",
"value": "Maxima Medisch Centrum"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/11/facility",
"value": "Groene Hart Ziekenhuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/11/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/12/facility",
"value": "Spaarne Gasthuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/13/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/14/facility",
"value": "Tergooi Ziekenhuizen"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/14/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/18/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/19/facility",
"value": "Laurentius Ziekenhuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/19/city",
"value": "Roermond"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/19/contacts/0/name",
"value": "K. Aaldering"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/19/geoPoint/lat",
"value": 51.19417
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/19/geoPoint/lon",
"value": 5.9875
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/20/facility",
"value": "Bravis Ziekenhuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/20/city",
"value": "Roosendaal"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/20/contacts/0/name",
"value": "H. Droogendijk"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/20/geoPoint/lat",
"value": 51.53083
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/20/geoPoint/lon",
"value": 4.46528
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/21",
"value": {
"city": "Rotterdam",
"status": "NOT_YET_RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "A. Jager",
"role": "CONTACT"
}
],
"facility": "Erasmus MC, Universitair Medisch Centrum Rotterdam",
"geoPoint": {
"lat": 51.9225,
"lon": 4.47917
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/22",
"value": {
"city": "Sneek",
"status": "NOT_YET_RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "G. Veldhuis",
"role": "CONTACT"
}
],
"facility": "Antonius Ziekenhuis",
"geoPoint": {
"lat": 53.03297,
"lon": 5.6589
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/23",
"value": {
"city": "The Hague",
"status": "RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "H. Oosterkamp",
"role": "CONTACT"
}
],
"facility": "Haaglanden Medisch Centrum",
"geoPoint": {
"lat": 52.07667,
"lon": 4.29861
}
}
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/24",
"value": {
"city": "The Hague",
"status": "RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "D. Houtsma",
"role": "CONTACT"
}
],
"facility": "HAGA Ziekenhuis",
"geoPoint": {
"lat": 52.07667,
"lon": 4.29861
}
}
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/26/facility",
"value": "Elisabeth Tweesteden Ziekenhuis"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/26/city",
"value": "Tilburg"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/26/contacts/0/name",
"value": "J. van Riel"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/26/geoPoint/lat",
"value": 51.55551
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/26/geoPoint/lon",
"value": 5.0913
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/27/facility",
"value": "VieCuri Medisch Centrum"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/27/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/27/city",
"value": "Venlo"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/27/contacts/0/name",
"value": "A. van de Wouw"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/27/geoPoint/lat",
"value": 51.37
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/27/geoPoint/lon",
"value": 6.16806
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/28/facility",
"value": "Streekziekenhuis Koningin Beatrix"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/28/status",
"value": "RECRUITING"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/28/city",
"value": "Winterswijk"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/28/contacts/0/name",
"value": "P. Schiphorst"
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/28/geoPoint/lat",
"value": 51.9725
},
{
"op": "replace",
"path": "/protocolSection/contactsLocationsModule/locations/28/geoPoint/lon",
"value": 6.71944
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/29",
"value": {
"city": "Zwolle",
"status": "NOT_YET_RECRUITING",
"country": "Netherlands",
"contacts": [
{
"name": "A. Honkoop",
"role": "CONTACT"
}
],
"facility": "Isala",
"geoPoint": {
"lat": 52.5125,
"lon": 6.09444
}
}
}
]