None listed
Conditions
Interventions
Group 1 Type of group
Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. + Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
Group name:Group 2 Type of group
Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. + Paclitaxel - 80 mg/m² IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
Sponsors
LABORATORIOS WYETH S.A.,
Eligibility
Sex/Gender
Female
Age
18 Years to 120 Years
Inclusion criteria
Inclusion criteria: • Female subjects from 18 years of age. • Diagnosis of breast cancer confirmed histologically or cytologically. • Metastatic or recurrent breast cancer at the local level that is not treatable with curative surgery or radiation. • Documentation of amplification of the erbB-2 gene by FISH (as defined by a proportion> 2.2) or in situ chromogenic hybridization (CISH, as defined in the kit manufacturer´s instructions) or overexpression of erbB-2 via IHC (defined as IHC3 + or IHC2 + with confirmation by FISH or CISH) according to local laboratory results or initial diagnosis using 1 of the trials approved by the sponsor. If erbB-2 status is not available or determined using a test other than the sponsor-approved trial and cannot be assessed using one of these trials before randomization, the test and study eligibility must be obtained from the central laboratory identified by the sponsor before randomization. • All patients should have tumor tissue (that is, the tissue with fixed insert in more recently archived formalin [block or unstained preparations]) for central revision of erbB-2 expression levels by FISH test performed by the Central laboratory identified by the sponsor. • Before entering the study, documentation of ER / PgR status (positive / negative according to local laboratory results or initial diagnosis should be available. If results are not available, tumor tissue may be sent to the central laboratory identified by the sponsor to evaluate it before entering the study according to the criteria of the researcher. • At least one quantifiable lesion, according to the Criteria of evaluation of the response in solid tumors (RECIST). • Status from O to 2 according to the Eastem Cooperative Oncology Group (ECOG) (not decreasing within 2 weeks prior to the signing of the informed consent). • Left ventricular ejection fraction (LVEF) within the normal institutional range, as measured by radioisotopic ventriculography (MUGA) or echocardiogram (ECHO). • Recovery (at level 1 or baseline) of all clinically significant acute adverse effects of previous therapies (not including alopecia). • All women who are not surgically sterile or postmenopausal should agree and commit to using a reliable contraceptive method from 2 weeks before the administration of the first dose of the product under investigation and up to 28 days after the last dose of the product in investigation. A woman with reproductive capacity is one who is in a biological position to conceive. This includes women who are using contraceptives or those whose sexual partners are sterile or use contraceptives.
Exclusion criteria
Exclusion criteria: • Previous systemic anti-cancer therapy (which includes cytotoxic chemotherapy, signal transduction inhibitors [for example, lapatinib], biological therapy [for example, trastuzumab] or other anti-cancer therapy under investigation) for metastatic or recurrent disease at the local level. Prior endocrine therapy is allowed in any context. • Previous treatment with an erbB-2 inhibitor, other than trastuzumab, lapatinib or the combination of both, in the neoadjuvant or adjuvant context. • Previous treatment with neoadjuvant or adjuvant anthracyclines with a cumulative dose of doxorubicin of> 400 mg / m ´´, epirubicin dose of> 800 mg / m or the equivalent dose of other anthracyclines or derivatives (for example, 72 mg / m ^ 2 of mitoxantrone). • Subjects with recurrent or progressive disease within 12 weeks after the end of a neoadjuvant or adjuvant systemic anticancer therapy (which includes cytotoxic chemotherapy, signal transduction inhibitors [eg, lapatinib], biological therapy [eg, trastuzumab ] or other anticancer therapy under investigation), other than endocrine therapy for early breast cancer. • Subjects in which bones or skin are the only focus of the quantifiable disease. Subjects with quantifiable skin lesions by computed tomography (CT) or magnetic resonance imaging (MRI) images, since only quantifiable disease sites are admitted. • Major surgery, chemotherapy, radiation therapy, any investigating agent or other cancer therapy within 2 weeks prior to the administration of the first dose of the product under investigation. • Uncontrolled or symptomatic active CNS metastasis, as indicated by clinical symptoms, cerebral edema or progressive growth. Subjects with a history of CNS metastasis or spinal cord compression are eligible if they have received definitive treatment and are not being treated with anticonvulsants and steroids for a minimum of 4 weeks prior to the first dose of the product under investigation. • Uncontrolled active heart disease, which includes cardiomyopathy, congestive heart failure (functional classification of> 3 of the New York Heart Association [NYHA]), unstable angina and myocardial infarction (within 12 months of admission to the study). • Inappropriate controlled hypertension (ie systolic blood pressure [BP]> 180 mm Hg or diastolic blood pressure> 100 mm Hg). • Family history of congenital long or short QT syndrome, Brugada syndrome or QT / QTc interval> 0.45 seconds or known history of prolongation of QT / QTc or torsade de pointe (TdP). • Significant chronic gastrointestinal disorder with diarrhea as the main symptom (for example, Crohn´s disease, malabsorption or diarrhea of ​​grade> 2 of any etiology at the beginning). • Pre-existing sensory or motor neuropathy grade 2 or higher. • History of hypersensitivity reaction with life risk to taxanes or trastuzumab. • Clinical contraindication of steroids that prevents its use as part of the premedication of paclitaxel. • Pregnant, breastfeeding women or women with reproductive capacity who are not using effective contraceptive methods during study participation and do not agree to use them for at least 28 days after the final dose of the product under investigation. • Impossibility or reluctance to swallow oral medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy. Measure:Progression-Free Survival Timepoints:From randomization to disease progression or death, assessed up to 5.3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-Progressive Disease for non-target lesions, and no new lesions. Measure:Objective Response Rate Timepoints:From randomization to disease progression or last tumor assessment, assessed up to 5.3 years ; Outcome name:Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, disease progression (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions. Measure:Duration of Response Timepoints:From first response to first PD or death, assessed up to 5.3 years after first subject randomized ; Outcome name:Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Measure:Clinical Benefit Rate Timepoints:From randomization to disease progression or d | — |
Countries
Arabia Saudi, Argentina, Australia, Bahamas, Belgium, Bulgaria, Canada, China, Colombia, Croatia, Denmark, France, Germany, Greece, Hong Kong, Hungaria, India, Israel, Italy, Japan, Korea South, Latovia, Latvia, Lebano, Lithuania, Malasya, MAlta, Mexico, Poland, Portugal, Romania, Serbia, Singapore, South Africa, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kindgdom, United States
Contacts
Public ContactJudith Marlene Verastegui
LABORATORIOS WYETH S.A.
Outcome results
None listed