A Randomized, Multicenter, Phase III Study Comparing the Combination of Pazopanib and Lapatinib versus Lapatinib Monotherapy in Patients with ErbB2 over-expressing Inflammatory Breast Cancer
- Registration Number
- PER-086-07
- Lead Sponsor
- GLAXOSMITHKLINE PERU S.A.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Sex
- Not specified
- Target Recruitment
- 11
• Histologic confirmation of breast carcinoma with a clinical diagnosis of IBC as the original diagnosis based on the presence of inflammatory changes in the breast involved, including diffuse erythema and edema (orange peel), with or without an underlying palpable mass. Pathological evidence of dermal lymphatic invasion should be noted but is not required for diagnosis. The documentation of the initial IBC diagnosis must be included in the original documentation.
• Progression or recurrence of the disease after treatment for IBC, which must have included a chemotherapy regimen. In regions where trastuzumab is available without impediments to access, patients must have previously received trastuzumab in addition to chemotherapy in order to be eligible.
• Tumor that overexpresses ErbB2 as defined based on at least one of the following local results: 1.) overexpression 3+ by IHC or 2.) amplification of the HER2 gene by FISH or CISH. Archived tumor tissue from all patients should be provided for ErbB2 exploration using FISH technology by the central laboratory. The central scan is for analysis only. Patients will remain in the study based on the results of local ErbB2 expression.
• Patients will have a radiographically quantifiable disease according to the Solid Tumor Response Evaluation Criteria (RECIST) [Therasse, 2000] or evaluable IBC cutaneous disease. If the only evidence of recurrent IBC is skin disease, a biopsy of the skin disease must have been performed at some time. Radiographically quantifiable lesions may be in the field of prior adjuvant irradiation; however, a period of at least 8 weeks must elapse between the last radiation treatment and the initial (baseline) scan that documents the state of the disease so that the lesion is quantifiable. If the irradiated lesion is the sole focus of the disease, documented progression of the irradiated lesion is required.
• Patients must give written informed consent before carrying out procedures or specific evaluations of the study and must be willing to comply with treatment and follow-up. The procedures conducted as part of the routine clinical treatment of the patient (for example, complete blood count, diagnostic imaging study) and obtained prior to signing the informed consent may be used for selection or initial evaluation purposes provided that these procedures are conducted in the manner specified in the protocol.
• Age> 18 years.
• Adequate organic function
• Fraction of cardiac ejection within the normal institutional range measured by the echocardiogram. MUGA scans will be accepted in cases in which an echocardiogram can not be performed or when it does not give conclusive results, or when MUGA scans are the accepted standard. Patients with a known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible.
• Archived tumor tissue from all patients should be provided.
• Degree of activity in the ECOG Scale of the Eastern Cooperative Oncology Group (Eastem Cooperative Oncology Group) = 0-2.
• A woman is eligible to enter and participate in this study if: She is infertile (ie, physiologically unable to procreate), including any woman who has had :, a hysterectomy, a bilateral ovariectomy), a bilateral tubal ligation, is post -menopausal
• Treatment with any therapy for cancer (surgery, tumor embolization, chemotherapy, radiotherapy, immunotherapy, biological therapy, or hormonal therapy) in the 14 days prior to randomization, or mitomycin treatment within 6 weeks prior to randomization. Such treatment can not be started or resumed after entry into the study. Note: Patients receiving therapy with LH-RH analogues prior to the study may continue to receive LHRH analogues for the duration of their participation in the study.
• Any ongoing toxicity from a previous anti-cancer therapy that is> Grade 1 and / or that is getting worse.
• Previous therapy with lapatinib.
• Use of an agent in the clinical research phase, including an anticancer agent under investigation, within a period of 28 days or five half-lives, whichever is longer, before the first dose of the product under investigation .
• Use of any prohibited medication within the periods indicated in Section 8.2.
• Evidence of active or recurrent disease of a previous cancer.
• History or clinical evidence of central nervous system (CNS) metastasis or leptomeningeal carcinomatosis, except for individuals who have had CNS metastases previously treated, are asymptomatic, and have not required steroids or anti-convulsant medication in the two months prior to first dose of the study medication. Selection with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastasis.
• Clinically significant gastrointestinal abnormalities that may increase the risk of: Active peptic ulcer, Inflammatory bowel disease, Ulcerative colitis, or other gastrointestinal conditions with an increased risk of perforation, History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess in the 28 days before the start of the treatment under study.
• Clinically significant gastrointestinal abnormalities that may affect the absorption of the investigational product including, but not limited to: Insufficient absorption syndrome (malabsorption), Major resection of the stomach or small intestine.
• Presence of uncontrolled infection.
• Prolongation of the corrected QT interval (QTc)> 480 msecs.
• History of one or more of the following cardiovascular conditions within the previous six months: • Angioplasty or stenting (cardiac stenting) • Myocardial infarction • Unstable angina • Congestive heart failure Class III or IV, as defined by the Society. New York Cardiology (NYHA) (See description in Section 15.7 Appendix 7).
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of> 40mraHg or diastolic blood pressure (DBP) of <90mmHg].
• History of stroke, pulmonary embolism or deep vein thrombosis (DVT) untreated within the previous 6 months.
• Previous major surgery or trauma within 28 days prior to the first dose of the investigational product and / or presence of any wound, fracture or ulcer with healing problems.
• Evidence of active hemorrhage or hemorrhagic diathesis.
• Hemoptysis within 6 weeks prior to the first dose of the product under investigation.
• Any medical condition, serious psychiatric and / or pre-existing unstable, or other condition that may interfere with safety, provision of informed consent or compliance with the study procedures by the patient.
• Response of immediate or delayed hypersensitivity known,
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:defined as the interval between the randomization date and the earliest date between the progression of the disease or death due to any cause.<br>Measure:Progression free survival<br>Timepoints:date of progression of the disease or death due to any cause.<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Global survival defined as the randomization date until death due to any cause. (This is a key secondary endpoint)<br>Measure:Global survival<br>Timepoints:After treatment<br>;<br>Outcome name:Defined as Complete Response + Partial Response<br>Measure:Target Response Rate<br>Timepoints:During treatment<br>;<br>Outcome name:Change in the State of Health since the initial evaluation.<br>Measure:Change in the State of Health since the initial evaluation.<br>Timepoints:After treatment<br>;<br>Outcome name:Incidence, severity and causality of Adverse Events (AE), Serious Adverse Events (SAEs) and other safety parameters.<br>Measure:Incidence, severity and causality of Adverse Events (AE), Serious Adverse Events (SAEs) and other safety parameters.<br>Timepoints:During treatment<br>