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 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.