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: 9.1Level: LLTClassification code 10021974Term: Inflammatory breast cancer

• Registration Number: EUCTR2006-006537-40-CZ
• Lead Sponsor: GlaxoSmithkline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-12-10
• Last Update Posted: 1 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 351

Inclusion Criteria

1.Patients must have Inflammatory Breast Cancer (IBC) either at original diagnosis or upon relapse (secondary IBC). Patients must have cutaneous disease (measurable and/or non-measurable) and/or non-cutaneous disease that is measurable according to RECIST. A cutaneous biopsy containing invasive breast cancer (which may be from an excisional biopsy, mastectomy specimen, or other cutaneous biopsy) at any timepoint concomitant with the clinical diagnosis of IBC is required for all patients prior to randomization.
See Protocol for further description of requirements to substantiate a diagnosis of IBC. (Note: All patients must have photography at screening. Screening photographs must be uploaded to the Canfield website, reviewed and approved before a patient can be randomized.)
2.Measurable lesions (cutaneous or radiographic) may be in the field of prior standard or palliative radiation therapy; however, there must be at least a 4 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.
3.Disease progression or relapse following treatment for invasive breast cancer, 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.
*(Barriers to access may include financial considerations)
4.Tumor that overexpresses ErbB2 as defined by at least one of the following based on local results: 1.) 3+ overexpression by IHC or 2.) unequivocal 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.
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.Females age = 18 years, except in Tunisia. In Tunisia, patients must be = 20 years to be eligible for this study.
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. If archived tumour tissue is not available, the optimal biopsy for biomarkers and/or cutaneous biopsy during screening may be used.
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 becomin

Exclusion Criteria

1.Patients with only non-cutaneous Inflammatory Breast Cancer that is not measurable by RECIST (eg. disease confined to the bone) and/or whose original diagnosis of IBC cannot be substantiated by all of the items outlined in the inclusion criteria
2.Treatment in the 14 days prior to randomization with any cancer therapy (tumor embolization, chemotherapy, 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. Biophosphonates are permitted if started prior to Day 1.
3.Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
4.Prior lapatinib therapy.
5.Prior therapy with an anti-VEGF antibody or targeted VEGF-R tyrosine kinase inhibitor.
6.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.
7.Use of any prohibited medication within the timeframes listed in Section 8.2.
8.Evidence of recurrence or active disease from prior malignancy (other than IBC).
9.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.
10.Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to:
•Active peptic ulcer disease
•Known intraluminal metastatic lesion/s with suspected bleeding
•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.
11.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.
12.Presence of uncontrolled infection.
13.Prolongation of corrected QT interval (QTc) > 480 msecs.
14.History of any one or more of the following cardiovascular conditions within the past 6 months:
•Cardiac angioplasty or stenting
•Myocardial infarction
•Unstable angina
•Arterial thrombosis
•Symptomatic peripheral vascular disease
•Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (See Section 15.7 Appendix 7 for description).
15.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 1 hour. 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified