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-DE
• Lead Sponsor: GlaxoSmithkline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-08-10
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

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

Inclusion Criteria

For Cohort 1 of this study, eligible patients met inclusion criteria outlined in the original version of the protocol and protocol amendment 1.

For Cohort 2 of this study, eligible patients must meet all of the following criteria:
1. Patients must have evaluable Inflammatory Breast Cancer (IBC) substantiated by all of the following prior to randomization:
• History of invasive breast cancer documented by a biopsy and accompanying pathology report
• Current photographs* (global view and close-up views of all skin lesions) submitted at screening demonstrating unequivocal evidence of IBC as determined by either the medical monitor alone or in consultation with one or more of the study Principal Investigators.
*All patients must have photography at screening. Canfield Scientific Inc. will provide centralized monitoring, tracking, and collection of patients' photographs throughout the study. Screening photographs must be uploaded to the Canfield Scientific Inc website and approved by Canfield Scientific Inc, as the central photography vendor. The photographs, along with the completed Inflammatory Breast Cancer Skin Assessment Tool (IBSAT), must be reviewed and approved by GSK before a patient can be randomized. Sites should allow a minimum of 3 business days for this process. Sites submitting quality photographs and IBSATs on a regular basis will receive an exemption from this requirement for future patients.
2.Patients with secondary IBC are eligible.
3.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.
4.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)
5.Unequivocal ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH/CISH, or ErbB2 gene amplification by FISH/CISH alone (in subjects whose tumor blocks were not assessed by IHC). ErbB2 gene amplification is defined by: > six (6) ErbB2 gene copies/nucleus for test systems without an internal control probe or an ErbB2/CEP 17 ratio of more than 2.2. Sites must submit a copy of the laboratory report demonstrating unequivocal ErbB2 overexpression, if testing performed at a local laboratory, with the screening worksheet. Archived tumor must be provided for all patients for ErbB2 FISH testing by the central laboratory. Patients will remain on study based on local ErbB2 expression results. If archived tumor is not available, a biopsy must be obtained at screening and sent to TMD Laboratoraties for ErbB2 FISH testing.
6.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 informe

Exclusion Criteria

1.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.
2.Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
3.Prior lapatinib therapy or other Her2/ErbB2 targeted therapy (except trastuzumab).
4.Prior therapy with an anti-VEGF antibody or targeted therapy
5.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.
6.Use of any prohibited medication within the timeframes listed in Section 8.2.
7.History of another malignancy. Note: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. If subject previously had breast cancer, it must have been HER2+ with either 3+ overexpression by IHC or unequivocal HER2 gene amplification by FISH or CISH.
8.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.
9.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.
10.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.
11.Presence of uncontrolled infection.
12.Prolongation of corrected QT interval (QTc) > 480 msecs.
13.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).
14.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

Study & Design

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