Inclusion Criteria

Inclusion criteria:

Specific information regarding warnings, precautions, contraindications, adverse events,
and other pertinent information on the investigational product that may impact patient
eligibility is provided in the pazopanib IB and lapatinib prescribing information (or the
lapatinib IB).

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:

- 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.

- Patients with secondary IBC are eligible.

- 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.

- 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.)

- 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
Laboratories for ErbB2 FISH testing.

- 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: Informed consent may be obtained prior to the protocol-specified screening window
(i.e. Day -14 to Day -1).

- Females age ≥ 18 years, except in Tunisia. In Tunisia, patients must be ≥ 20 years
to be eligible for this study.

- Adequate organ function as defined below:

- System (Laboratory Values)

- Hematologic:Absolute neutrophil count (ANC)(≥ 1.5 X 10^9/L)Hemoglobin1(≥9
g/dL)Platelets(≥100 X 10^9/L)International normalized ratio (INR)(≤ 1.2 X upper
limit of normal (ULN))Partial thromboplastin time (PTT)(≤1.2 X ULN)

- Hepatic:Total bilirubin2 (≤ 1.5 X upper limit of normal (ULN))AST and ALT(≤ 2.5 X
ULN)

- Renal:Serum Creatinine (≤ 1.5 mg/dL)Or, if serum creatinine >1.5 mg/dL,

- Calculated creatinine clearance(≥50 mL/min)

- Urine Protein to Creatinine Ratio(<1)

- Patients may not have had a transfusion within 7 days of screening assessment.

- Exception: Patients with elevated bilirubin levels due to Gilberts syndrome are
eligible.

- 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.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- 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 bilateral tubal ligation

- Is post-menopausal

- Patients not using hormone replacement therapy (HRT) must have experienced total
cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in
questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an
estradiol value < 40pg/mL (<140 pmol/L).

Patients must discontinue HRT prior to study enrollment due to the potential for
inhibition of CYP enzymes that metabolize estrogens and progestins (See Section 8). For
most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and
determination of menopausal status; length of this interval depends on the type and dosage
of HRT. If a female patient is determined not to be post-menopausal, they must use
adequate contraception, as defined immediately below.

Childbearing potential, including any female who has had a negative serum pregnancy test
within 2 weeks prior to the first dose of study treatment, preferably as close to the
first dose as possible, has used adequate contraception since the pregnancy test and
agrees to use adequate contraception as described below. GSK acceptable contraceptive
methods, when used consistently and in accordance with both the product label and the
instructions of the physician, are as follow:

- An 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 (condom with spermicidal jelly, foam suppository, or
film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

Note: Oral contraceptives are not reliable due to potential drug drug interactions.

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.

- French patients: In France, a patient will be eligible for inclusion in this study only
if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

- Patients meeting any of the following criteria must not be enrolled in the study:

- 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. Bisphosphonates are permitted if started prior to Day 1.

- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity (with the exception of alopecia).

- Prior lapatinib therapy or other Her2/ErbB2 targeted therapy (except trastuzumab).

- Prior therapy with an anti-VEGF antibody or other VEGF/VEGF-R targeted therapy.

- 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.

- Use of any prohibited medication within the timeframes listed in Section 8.1.3

- 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.

- 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.

- 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.

- 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.

- Presence of uncontrolled infection.

- Prolongation of corrected QT interval (QTc) > 480 msecs.

- 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 15.9 Appendix 9 for description).

- 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 during the
screening period, in order to control a patient's BP prior to randomization. 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 Section 6.2 and Section 6.4.2 for
details on blood pressure control and reassessment prior to study enrollment.

- History of cerebrovascular accident, including TIA, pulmonary embolism or deep venous
thrombosis (DVT).

- 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 (other than
ulcers due to inflammatory breast cancer).

- Evidence of active bleeding or bleeding diathesis.

- Hemoptysis within 6 weeks prior to first dose of investigational product.

- Known endobronchial lesions or involvement of large pulmonary vessels by tumor.

- 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.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib or lapatinib.

- Have current active hepatic or biliary disease (with exception of patients with
Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
disease per investigator assessment).