Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer

Inclusion Criteria:

   - A subject will be eligible for inclusion in this study only if all of the following
   criteria are met:

   - Signed, written informed consent prior to performing any study-related procedures

   - Female subjects ≥18 years of age

   - FIGO Stage IVB, or recurrent or persistent cervical cancer

   - Life expectancy of at least 12 weeks

   - ECOG status of 0 or 1.

   - Histologically confirmed FIGO Stage IVB, or recurrent or persistent squamous cell
   carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not
   amenable to curative treatment with surgery and/or radiation therapy

   - Measurable disease, defined as at least one lesion that can be accurately measured in
   at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm
   when measured by conventional techniques, including palpitation, plain x-ray, CT and
   MRI, or ≥10 mm when measured by spiral CT.

   - At least one "target lesion" to be used to assess response as defined by Response
   Evaluation Criteria in Solid Tumors (RECIST; Terasse, 2000). Tumors within a
   previously irradiated field will be designated as "non-target" lesions unless
   progression is documented or a biopsy is obtained to confirm persistence at least 90
   days following completion of radiation therapy.

   - Received 0 or 1 prior chemotherapy regimen for metastatic disease.

   - Note: Chemotherapy given in combination with radiation therapy as a radiosensitizer
   does not count toward this prior therapy limit

   - Recovered from the effects of surgery or chemotherapy. At least three weeks must have
   elapsed from the last administration of chemotherapy.

   - Adequate organ and bone marrow function as defined in Table 1.

   - Table 1:(Definitions for Adequate Organ Function)

   - System:(Laboratory Values)

   - Hematologic: Absolute neutrophil count (ANC)(≥ 1.5 X 109/L)Hemoglobin1(≥9
   g/dL)Platelets(≥100 X 109/L)

   - Hepatic: Total bilirubin (≤1.5 X ULN)AST and ALT (≤2.5 X ULN)

   - Renal: Calculated creatinine clearance2 (≥50 mL/min)

   - Urine protein3 (Negative, trace or +1 by dipstick urinalysis or <1.0 gram determined
   by 24 hour urine protein analysis.)

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

   - Calculated by Cockcroft Gault formula See Appendix 7: Renal Function Tests

   - A patient should first be screened with dipstick urinalysis. If urine protein by
   dipstick analysis is ≥2+, then a 24-hour urine protein must be assessed and 24 hour
   urine protein must be <1 g protein to be eligible.

   - Ability to swallow and retain oral medication.

   - 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 (total cessation of menses for ≥ 1 year)

   - Childbearing potential, has 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,
   and agrees to use adequate contraception. GSK acceptable contraceptive methods, when
   used consistently and in accordance with both the product label and the instructions
   of the physician, are as follows:

   - An intrauterine device with a documented failure rate of less than 1% per year.

   - Vasectomized partner who is sterile prior to the female subject's entry and is the
   sole sexual partner for that female.

   - Complete abstinence from sexual intercourse for 14 days before exposure to
   investigation 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.

   - Subjects 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
   as outlined in the protocol. Procedures conducted as apart of routine clinical
   management of the patient (e.g., blood count, imaging study) and obtained prior to
   signed informed consent may be utilized for screening purposes provided these tests
   are obtained as specified in the protocol

Exclusion Criteria:

   - A subject will not be eligible for inclusion in this study if any of the following
   criteria apply:

   - Neuroendocrine or small cell carcinoma of the cervix.

   - Prior use of any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors.

   - Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy,
   biologic therapy, hormonal therapy, and tumor embolization).

   - Concurrent treatment with an investigational agent or participation in another
   clinical trial.

   - Use of an investigational anti-cancer drug within 28 days or 5 half-lives, whichever
   is longer, preceding the first dose of study medication.

   - Has taken or is taking prohibited medications listed in the protocol.

   - Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
   that could interfere with patient's safety, obtaining informed consent or compliance
   to the study.

   - History of another malignancy. Note: Patients who have had another malignancy and have
   been disease-free for 5 years, or patients with a history of completely resected
   non-melanomatous skin carcinoma or successfully treated in situ carcinoma are
   eligible.

   - History or clinical evidence of central nervous system (CNS) metastases or
   leptomeningeal carcinomatosis. Routine screening with CNS imaging studies (computed
   tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically
   indicated.

   - Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or
   resection of the stomach or small bowel.

   - Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal
   condition increasing the risk of perforation; history of abdominal fistula,
   gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to
   beginning therapy.

   - Presence of uncontrolled infection.

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

   - Corrected QT interval (QTc) prolongation defined as QTc interval > 470 msecs.

   - History of any one of the following cardiac conditions within the past 6 months:

   - Cardiac angioplasty or stenting

   - Myocardial infarction

   - Unstable angina

   - History of cerebrovascular accident or pulmonary embolus within the past 6 months.

   - Has Class III or IV heart failure as defined by the New York Heart Association (NYHA)
   functional classification system (See Appendix 6)

   - Poorly controlled hypertension (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. The blood pressure (BP) must be re-assessed on two occasions that are
   separated by a minimum of 24 hours. The mean SBP/DBP values from both BP assessments
   must be < 140/90mmHg in order for a subject to be eligible for the study.

   - History of untreated deep venous thrombosis (DVT) within the past 6 months (e.g. calf
   vein thrombosis).

   - Note: Patients with recent DVT who are treated with therapeutic anti-coagulant agents
   (excluding therapeutic warfarin) for at least 6 weeks are eligible.

   - Presence of any non-healing, non-tumor related wound, fracture, or ulcer, or the
   presence of symptomatic peripheral vascular disease.

   - Subjects with bilateral hydronephrosis which cannot be alleviated by ureteral stents
   or percutaneous drainage.

   - Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks
   prior to beginning therapy, or anticipation of the need for a major surgical procedure
   during the course of the study; minor surgical procedures such as fine needle
   aspiration or core biopsy within 1 week prior to beginning therapy are also excluded.

   - Unable to swallow and retain orally administered medication.

   - Pregnant or lactating female.