| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or refractory inflammatory breast cancer with ErbB2 tumors |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10021977 |
| E.1.2 | Term | Inflammatory carcinoma of breast recurrent |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to compare the progression-free survival between pazopanib in combination with lapatinib versus lapatinib alone in patients with relapsed or refractory IBC whose tumors overexpress ErbB2. |
|
| E.2.2 | Secondary objectives of the trial |
| To compare overall survival (OS) between patients treated with lapatinib and pazopanib combination therapy versus patients treated with lapatinib alone.To compare objective response rate (ORR, defined as CR + PR) and response duration after treatment with the combination of lapatinib and pazopanib versus lapatinib alone.To compare the safety and tolerability of the two regimens.To compare health status assessments between the two regimens. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1.Histological confirmation of breast carcinoma with a clinical diagnosis of IBC at original diagnosis based on the presence of inflammatory changes in the involved breast.Documentation of initial diagnosis of IBC must be included in source documentation.
2.Disease progression or relapse following treatment for IBC, which must have included a chemotherapy regimen.In regions where trastuzumab is available with no barriers to access, patients must have received prior trastuzumab in addition to chemotherapy in order to be eligible.
3.Tumor that overexpresses ErbB2 as defined by at least one of the following based on local results: 1.) 3+ overexpression by IHC or 2.) HER2 gene amplification by FISH or CISH. Central testing is for analysis only.
4.Patients will have radiographically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) [Therasse, 2000] or evaluable IBC cutaneous disease.
5.Patients must provide written informed consent prior to performance of study-specific procedures.
6.Age ≥ 18 years.7. Adequate organ function 8.Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram or MUGA. Patients with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible.
9.Archived tumor tissue must be provided for all patients.
10.ECOG performance status of 0-2.
11.A female is eligible to enter and participate in this study if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: hysterectomy,bilateral oophorectomy (ovariectomy),bilateral tubal ligation,post-menopausal
Patients must discontinue HRT prior to study enrollment due to the potential for inhibition of CYP enzymes. If a female patient is determined not to be post-menopausal, they must use adequate contraception, as defined below.GSK acceptable contraceptive methods are:intrauterine device with a documented failure rate of less than 1% per year,Vasectomized partner who is sterile prior to the female patient’s entry and is the sole sexual partner for that female, Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product,Double-barrier contraception Note: Oral contraceptives are not reliable due to potential drug drug interaction. Female patients who are lactating should discontinue nursing prior to the first dose of investigational product and should refrain from nursing throughout the treatment period and for 14 days following the last dose of investigational product. |
|
| E.4 | Principal exclusion criteria |
1.Treatment in the 14 days prior to randomization with any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy) Note: Patients receiving LH-RH analogue therapy prior to the study may continue to receive LH-RH analogues for the duration of study participation. 2. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
3.Prior lapatinib therapy.4.Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product.
5.Use of any prohibited medication as listed in Section 8.2. 6.Evidence of recurrence or active disease from prior malignancy.7.History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for CNS metastases 8.Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding
9. Clinically significant gastrointestinal abnormalities
10.Presence of uncontrolled infection.
11.Prolongation of corrected QT interval (QTc) > 480 msecs.
12.History of any one or more of the following cardiovascular conditions within the past 6 months:Cardiac angioplasty or stenting, Myocardial infarction,Unstable angina,Class III or IV congestive heart failure, as defined by NYHA 13.Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]. The mean SBP / DBP values from each blood pressure assessment must be < 140/90mmHg in order for a patient to be eligible for the study.
14.History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. 15.Prior major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer
16.Evidence of active bleeding or bleeding diathesis. 17.Hemoptysis within 6 weeks prior to first dose of investigational product.18.Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient’s safety, provision of informed consent, or compliance to study procedures.
19.Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or lapatinib. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PFS defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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