patients with triple-negative breast cancer, patients with HER2-positive early breast cancer MedDRA version: 14.1 Level: LLT Classification code 10021976 Term: Inflammatory breast cancer stage IV System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10063104 Term: Tubular breast cancer stage II System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 100000004864 MedDRA
Conditions
Interventions
Product Name: Carboplatin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CARBOPLATIN
CAS Number: 41575-94-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentra
Sponsors
German Breast Group GBG Forschungsgesellschaft mbH (Sponsor nach GCP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures. 2.Complete baseline documentation must be submitted via Medcodes® and approved by GBG Forschungs GmbH. 3.Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not allowed. In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint. 4.Tumor lesion in the breast with a palpable size of = 2 cm or a sonographical size of = 1 cm in maximum diameter. The lesion has to be measurable in two dimensions, preferably by sonography. In case of inflammatory disease, the extent of inflammation can be used as measurable lesion. 5.Patients should be in the following stages of disease: - cT2 - cT4a-d or - cT1c and cN+ or pNSLN+ 6.In patients with multifocal or multicentric breast cancer, the largest lesion should be measured. 7.Centrally confirmed ER/PR/HER-2 and Ki-67 status detected on core biopsy. ER/PR positive is defined as >1% stained cells and HER2-positive is defined as HercepTest IHC 3+ or FISH ratio =2.2. Formalin-fixed, paraffin-embedded (FFPE) breast tissue from core biopsy has therefore to be sent to the Dept. of Pathology at the Charité, Berlin prior to randomization (4 cores and up to 8-10mm FFPE tumor need to be provided). 8.Age = 18 years. 9.Karnofsky Performance status index = 80%. 10.Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 3 months prior to randomization. LVEF must be = 55%. 11.Laboratory requirements: Hematology - Absolute neutrophil count (ANC) = 2.0 x 109 / L and - Platelets = 100 x 109 / L and - Hemoglobin = 10 g/dL (= 6.2 mmol/L) Hepatic function -Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 600
Exclusion criteria
Exclusion criteria: 1.Prior chemotherapy for any malignancy. 2.Prior radiation therapy for breast cancer. 3.Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment. 4.Inadequate general condition (not fit for anthracycline-taxane-targeted agents-based chemotherapy). 5.Previous malignant disease without being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer). 6.Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >160 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease. 7.Previous thromboembolic event (except when thrombophily screening is negative). 8.Known hemorrhagic diathesis or coagulopathy with increased bleeding risk. 9.History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent 10.Pre-existing motor or sensory neuropathy of a severity = grade 2 by NCI-CTC criteria v 4.0. 11.Currently active infection. 12.Active peptic ulcer. 13.Incomplete wound healing or unhealed bone fracture. 14.Disease significantly affecting gastrointestinal function, e.g. malabsorption syndrome, resection of the stomach or small bowel, ulcerative colitis. 15.History of abdominal fistula or any grade 4 non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment. 16.Severe pulmonary condition / illness. 17.Major surgery within the last 28 days or anticipation of the need for major surgery during study treatment with bevacizumab. No minor surgeries including insertion of an indwelling catheter or sentinel lymph node biopsy within 24 h prior to chemotherapy. 18.Definite contraindications for the use of corticosteroids except inhalative corticoids. 19.Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol; 20.Concurrent treatment with: - chronic corticosteroids unless initiated > 6 months prior to study entry and at low dose (= 10 mg methylprednisolone or equivalent). - sex hormones. Prior treatment must be stopped before study entry. - virostatic agents like sorivudine or analogs like brivudine, concurrent treatment with aminoglycosides. - anticoagulants: heparin, warfarin as well as acetylic acid (e.g. Aspirin®) at a dose of > 325 mg/day or clopidogrel at a dose of > 75 mg/day. - other experimental drugs or any other anti-cancer therapy. - drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A, e.g. Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Ritonavir, Telithromycin, Erythromycin, Verapamil, Diltiazem within the last 5 days or the expected need for these treatments during study participation. 21.Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry. 22.Male patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment of combined cytotoxic-targeted therapy with or without carboplatin in patients with HER2-positive or triple-negative early breast cancer;Secondary Objective: •pCR rates per arm •toxicity and compliance •Comparison of efficacy and tolerability of the carboplatin given at AUC 2.0 or 1.5 •response rates of the breast tumor and axillary nodes based on physical examination and sonography, mammography or MRI, after treatment in both arms •rates of ypT0/is ypN0; ypT0; ypT0/is; ypN0; and regression grades •breast and axilla conservation rate after each treatment •LRRFS, RRFS, LRFS, DDFS, IDFS and overall survival in both arms •pCR rate and LRFS in patients with a clinical complete response and a negative core biopsy before surgery •response (complete vs. partial vs. no change) measured by best appropriate imaging method after the first two cycles of treatment with pCR •pCR rate in patients with a cCR and a negative core biopsy before surgery •RRFS in patients with initial node-positive axilla converted to negative at surgery and treated with sentinel node biopsy alone •examine and compare pre-specified molecular markers ;Primary end point(s): Pathological complete response of breast and lymph nodes (ypT0 ypN0; primary endpoint) ;Timepoint(s) of evaluation of this end point: Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. Surgery takes place shortly after the 18 weeks (six 3-week cycles) chemotherapy treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.ypT0/is ypN0; ypT0; ypT0/is; ypN0, and regression grade, response by physical examination, imaging response, breast conservation 2. Clinical (c) and imaging (i) response will be assessed by physical examination and imaging tests. 3. loco-regional invasive recurrence free survival (LRRFS), regional recurrence free survival (RRFS), local recurrence free survival (LRFS), distant-disease- free survival (DDFS), invasive disease-free survival (IDFS), and overall survival (OS) 4. Tolerability and Safety: Descriptive statistics for the 4 treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped 5. Translational research: Exploratory analyses will be performed to identify possible relationships between biomarkers and drug activity.;Timepoint(s) of evaluation of this end point: 1.Clinical (c) and imaging (i) response will be assessed in the 3rd week of cycle 2 (week 6) and cycle 6 (week 18) by physical examination and imaging tests. 2. in the 3rd week of cycle 2 and cycle 6 3. LRRFS, RRFS, LRFS, DDFS, IDFS and OS are defined as the time period between registration and first event 4. throughout the 18 weeks treatment period and the 30 day safety follow up 5. with core examination and with surgery. In addition and optional after 2nd cycle, before and after surgery | — |
Countries
Germany
Contacts
Public ContactGepar Sixto
GBG Forschungs GmbH
Outcome results
None listed