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
- Conditions
- Relapsed or refractory inflammatory breast cancer with ErbB2 tumours.MedDRA version: 9.1 Level: LLT Classification code 10021974 Term: Inflammatory breast cancer
- Registration Number
- EUCTR2006-006537-40-FR
- Lead Sponsor
- GlaxoSmithkline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
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, including diffuse erythema and edema (peau d’orange), with or without an underlying palpable mass. Pathologic evidence of dermal lymphatic invasion should be noted but is not required for diagnosis. 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. Archived tumor tissue must be provided for all patients for ErbB2 FISH testing by the central laboratory. Central testing is for analysis only. Patients will remain on study based on local ErbB2 expression results.
4.Patients will have radiographically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) [Therasse, 2000] or evaluable IBC cutaneous disease. If the only evidence of recurrent IBC is cutaneous disease, the cutaneous disease must have been biopsied at some time.
Radiographically measurable lesions may be in the field of prior adjuvant irradiation; however, there must be at least an 8 week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable. If the irradiated lesion is the only site of disease, documented progression of the irradiated lesion is required.
5.Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the patient’s routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
Note: It is not necessary that informed consent be obtained within the protocol-specified screening window.
6.Age = 18 years.
7.Adequate organ function as defined in Table 1 of the protocol
8.Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive or where MUGA scans are the accepted standard. 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.Eastern Cooperative Oncology Group (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:
•A hysterectomy
•A bilateral oophorectomy (ovariectomy)
•A bil
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) or treatment with mitomycin within 6 weeks prior to randomization. Such treatment may not be resumed or begun after study entry. 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 within the timeframes 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 individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to first dose of study drug. Screening 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 metastases.
8.Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to:
•Active peptic ulcer disease
•Inflammatory bowel disease
•Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
•History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
9.Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but limited to:
•Malabsorption syndrome
•Major resection of the stomach or small bowel.
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 the New York Heart Association (NYHA) (See Section 15.7 Appendix 7 for description).
13.Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140mmHg or diastolic blood pressure (DBP) of = 90mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on two occasions that are separated by a minimum of 24 hours. 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. See Sections 6.2 and 6.4.2 for details on blood pressure control and reassessment prior to study enrollment.
14.History
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method