RANDOMIZED, MULTICENTER, OPEN, PHASE III,STUDY OF LAPATINIB, TRASTUZUMAB AND ITS COMBINATION IN NEOADYUVANCIA MORE PACLITAXEL IN WOMEN WITH PRIMARY BREAST CANCER HER2 / ERBB2 POSITIVE
- Conditions
- -C509 Breast, unspecifiedBreast, unspecifiedC509
- Registration Number
- PER-089-07
- Lead Sponsor
- OVARTIS BIOSCIENSES PERU S.A.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 38
• Female sex;
• Age 18 years;
• Functional status ~ Eastern Cooperative Oncology Group (ECOG) 0-1 (see Appendix 2);
• Invasive breast cancer confirmed histologically: - primary tumor greater than 2 cm in diameter, measured by mammography and ultrasound, - any N, - no evidence of metastasis (MO) (supraclavicular ganglion involvement is allowed alone);
• Over-expression and / or amplification of HER2 in the invasive component of the primary tumor according to one of the following definitions [Wolff et al 2006] and confirmed by a laboratory certified before the random distribution (see Section 5.2): - 3+ overexpression by IHC (> 30% of invasive tumor cells); - overexpression 2+ or o + (in 3U% or less neoplastic cells) by IHC and in situ Hybridization test (FISH / CISH) demonstrating amplification of the HER2 gene; - Amplification of the HER2 gene by FISH / CISH (> 6 copies of the HER2 gene per nucleus or a FISH index [copies of the HER2 gene to signals on chromosome 17] of> 2.2.) Subjects with negative or equivocal general results ( index of the FISH test of <2.2, <6.0 copies of the HER2 gene per nucleus) and O, 1+, 2+ or 3+ staining scores (in 30% or less of the neoplastic cells) per IHC they are not eligible for participation in the Study.
• Misleading local results from non-certified laboratories can be sent for a final determination in a certified laboratory.
• The status of ErbB2 should be studied in certified local or regional laboratories prior to randomisation. If a local FISH test is performed in non-certified laboratories, the Path´Vysion (Vysis) or INFORM HER2 / neu (Inc. Window) test should be used, but they will also need confirmation of the results by a certified laboratory. IHC over-expression scores obtained locally will also require confirmation from a certified laboratory to be considered as entry criteria. Subjects with negative FISH / CISH local tests (test score <1.8, <4.0 copies of the ErbB2 gene per nucleus) or with IHC scores O and 1+ are not eligible for participation in the Study. Positive local FISH tests (> 6 copies of the ErbB2 gene per core or a FISH index of more than 2.2) or 2/3 + overexpression by the IHC obtained in non-certified local laboratories, must be confirmed in one of the certified laboratories before of the random distribution;
• Hormone receptor (HR) status: - The status of the estrogen receptor (ER) must be known.
• Hematopoietic status: - Absolute neutrophil count> 1.5 x 10 9/1, - Platelet count> 100 x 10 9/1, - Hemoglobin of at least 9 g / dl,
• Hepatic status: - Bilirubin • Kidney status: - Creatinine • Cardiovascular: - baseline LVEF> 50% measured by echocardiography (ECHO) or controlled multiple-scan study (MUGA),
• Serum negative pregnancy test, within 2 weeks (preferably 7 days) prior to randomization (for women with reproductive potential)
• Fertile subjects should use effective contraception (barrier method - condoms, diaphragm - also together with spermicidal gel or total abstinence - oral, injectable or implantable hormonal contraceptives are not allowed)
• Final informed consent form (FCI)
• The subject agrees to deliver samples of the tumor to send to the central laboratory and perform translational studies as part of this protocol
• Administration of pre-treatment for invasive primary breast cancer;
• History of another malignant disease. However, participants with a past or current history of squamous and basal carcinoma of completely resected skin or subjects successfully treated for carcinoma in situ of the cervix are eligible;
• Diagnosis of inflammatory breast cancer;
• Bilateral cancer;
• Multifocal cancer;
• Known antecedents of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, uncontrolled hypertension (> / = 180 / l 10), unstable diabetes mellitus, dyspnea at rest or chronic treatment with oxygen;
• Illness or concomitant condition that would make the subject unsuitable for participation in the study or any serious medical condition that could interfere with the subject´s safety;
• Serious unresolved or unstable adverse events from the previous administration of another investigational product;
• Active or uncontrolled infection;
• Dementia, altered mental state or any psychiatric condition that could impede the understanding or grant of the FCI;
• Malabsorption syndrome, disease that. Significantly affect gastrointestinal function, or resection of the stomach or small intestine. Subjects with ulcerative colitis are also excluded;
• Therapy for concurrent neoadjuvant cancer (chemotherapy, radiation therapy, immunotherapy, biological therapy, different from the treatments of the Study);
• Concomitant treatment with a drug in research or participation in another therapeutic clinical study;
• Reaction of immediate or delayed hypersensitivity known or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or its excipients;
• Pregnant or breastfeeding women;
• Concomitant use of inhibitors or inducers of CYP3A4 (see Section 7.2 for the list of prohibited medications).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Surgical specimens of breast and axillary lymph node resection will be evaluated for pathological tumor response, according to the NSABP guidelines<br>Measure:Complete pathological response<br>Timepoints:After treatment<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:It will be evaluated by clinical examination and by mammography and mammary ultrasound with two-dimensional measurements,<br>Measure:Tumor response<br>Timepoints:During treatment<br>;<br>Outcome name:It will be evaluated using the WHO criteria<br>Measure:Objective response<br>Timepoints:During treatment<br>