Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Pazopanib; Sunitinib
Intervention description: 800 mg administered once daily orally continuous dosing; 50 mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment
Intervention MeSH terms: Sunitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 927.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SUTENT; Locally advanced and/or metastatic renal cell carcinoma; Pazopanib; Sunitinib; GW786034; Renal cell carcinoma

Summary:

      This study is being conducted to provide a direct comparison of the efficacy, safety and
      tolerability for pazopanib and sunitinib (SUTENT)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Diagnosis of renal cell carcinoma with clear-cell component histology.

          -  Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy,
             bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or
             metastatic RCC

          -  Locally advanced or metastatic renal cell carcinoma

          -  Measurable disease by CT or MRI

          -  Karnofsky performance scale status of >=70

          -  Age >=18 years

          -  A female is eligible to enter and participate in this study if she is of:
             non-childbearing or agrees to use adequate contraception.

          -  Adequate organ system function

          -  Total serum calcium concentration <12.0mg/dL

          -  Left ventricular ejection fraction >= lower limit of institutional normal.

        Exclusion Criteria:

          -  Pregnant or lactating female (unless agrees to refrain from nursing throughout the
             treatment period and for 14 days following the last dose of study)

          -  History of another malignancy (unless have been disease-free for 3 years)

          -  History or clinical evidence of central nervous system (CNS) metastases (unless have
             previously-treated CNS metastases and meet all 3 of the following criteria are: are
             asymptomatic, have had no evidence of active CNS metastases for >=6 months prior to
             enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants)

          -  Clinically significant gastrointestinal abnormalities including, but not limited to:
             malabsorption syndrome, major resection of the stomach or small bowel that could
             affect the absorption of study drug, 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.

          -  Presence of uncontrolled infection.

          -  Prolongation of corrected QT interval (QTc) > 480 milliseconds

          -  History of any one or more of the following cardiovascular conditions within the past
             12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina,
             coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class
             III or IV congestive heart failure, as defined by the New York Heart Association

          -  History of cerebrovascular accident including transient ischemic attack within the
             past 12 months

          -  History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the
             past 6 months (unless had recent DVT and have been treated with therapeutic
             anti-coagulating agents for at least 6 weeks)

          -  Poorly controlled hypertension (defined as systolic blood pressure of >=150mmHg or
             diastolic blood pressure of >=90mmHg). Initiation or adjustment of antihypertensive
             medication(s) is permitted prior to study entry

          -  Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
             presence of any non-healing wound, fracture, or ulcer.

          -  Evidence of active bleeding or bleeding susceptibility

          -  Spitting/coughing up blood within 6 weeks of first dose of study drug

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

          -  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.

          -  Use any prohibited medications within 14 days of the first dose of study medication.

          -  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 study
             drug.

          -  Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors
             (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg.
             temsirolimus, everolimus, etc).

          -  Is now undergoing and/or has undergone in the 14 days immediately prior to first dose
             of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy,
             radiation therapy, immunotherapy, biological therapy, or hormonal therapy)

          -  Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
             progressing in severity.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to pazopanib or sunitinib.