Patient Preference Study of Pazopanib Versus Sunitinib in Advanced or Metastatic Kidney Cancer
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: pazopanib; sunitinib
Intervention description: oral anti-angiogenic treatment; oral anti-angiogenic treatment
Intervention MeSH terms: Sunitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 169.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: renal cell carcinoma; Votrient; cancer; pazopanib; patient preference; quality of life

Summary:

      This is a randomised, double-blind, cross-over study of pazopanib versus sunitinib in
      patients with locally advanced or metastatic renal cell carcinoma (mRCC) who have received no
      prior systemic therapy for advanced or metastatic RCC. Approximately 160 eligible patients
      will be stratified based on the ECOG performance status (0 vs. 1) and number of metastatic
      sites of disease (0 and 1 vs. >=2). The study consists of two treatment periods of 10 weeks
      with a 2-week wash-out period between the two treatment periods. Patients will receive
      pazopanib and sunitinib treatment sequentially in a double-blinded fashion. The primary
      objective of the study is to assess how the tolerability and safety differences between
      pazopanib and sunitinib translate into patient preference, defined by the patient's stated
      preference for which drug they may prefer to continue treatment with at end of study. The
      secondary objectives are to evaluate the reason for patient preference as assessed by a
      patient preference questionnaire; to evaluate fatigue as assessed by FACIT-Fatigue and
      quality of life as assessed by EuroQoL EQ-5D; to evaluate dose modifications and time to dose
      modification; and to evaluate safety.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must provide written informed consent prior to performance of any
             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 utilised for screening or baseline purposes provided these procedures
             are conducted as specified in the protocol.

          -  Received no prior systemic therapy (including interleukin-2, interferon-alpha,
             chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for
             advanced or metastatic RCC. Patients who received adjuvant treatment with a cancer
             vaccine are eligible.

          -  Locally advanced (defined as disease not amenable to curative surgery or radiation
             therapy) or metastatic renal cell carcinoma of any histology (equivalent to Stage IV
             RCC according to AJCC staging). Patients with non-measurable disease are allowed if
             metastatic disease can be confirmed.

          -  ECOG PS of 0 or 1

          -  Age >= 18 years

          -  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)
        Childbearing potential, including any female who has had a negative serum pregnancy test
        within two weeks prior to the first dose of study treatment, preferably as close to the
        first dose as possible and agrees to use adequate contraception.

          -  Adequate organ system functions

          -  Total serum calcium concentration <12.0mg/dL

          -  Left ventricular ejection fraction (LVEF) >=lower limit of institutional normal (LLN)
             as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan. The same
             modality used at baseline must be applied for subsequent evaluations.

          -  Patient is able to swallow and retain oral tablets

        Exclusion Criteria:

          -  Poor MSKCC risk group

          -  History of another malignancy. Note: Patients who have had another malignancy and have
             been disease-free for 3 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.

        Note: Patients who have previously-treated CNS metastases (surgery +/- radiotherapy,
        radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:

          -  Are asymptomatic,

          -  Have had no evidence of active CNS metastases for >=6 months prior to enrolment ,

          -  Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC).

          -  Any clinically significant gastrointestinal abnormalities that may increase the risk
             for gastrointestinal bleeding or affect absorption of investigational product
             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

          -  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.

          -  Corrected QT interval (QTc) >480 msecs using Bazett's formula

          -  History of one or more of the following cardiovascular conditions within the past 6
             months:

          -  Cardiac angioplasty or stenting

          -  Myocardial infarction

          -  Unstable angina

          -  Coronary artery bypass graft surgery

          -  Symptomatic peripheral vascular disease

          -  Class III or IV congestive heart failure, as defined by the New York Heart Association
             (NYHA)

          -  Poorly controlled hypertension (defined as systolic blood pressure (SBP) of > 150mmHg
             or diastolic blood pressure (DBP) of > 90mmHg) at baseline.

        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 within a visit. The mean SBP/DBP values from each blood pressure
        assessment must be <=150/90mmHg in order for a patient to be eligible for the study.

        - History of cerebrovascular accident (CVA) including transient ischemic attack (TIA),
        pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

        Note: Patients with recent DVT who have been treated with therapeutic anti-coagulating
        agents for at least 6 weeks are eligible.

          -  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 (procedures such as catheter
             placement not considered to be major).

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.

          -  Evidence of active bleeding or bleeding diathesis.

          -  Significant haemoptysis within 6 weeks prior to first dose of study drug.

          -  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.

          -  Radiation therapy, surgery or tumour embolisation within 14 days prior to the first
             dose of study treatment.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to pazopanib or sunitinib.

          -  Pregnant or lactating female Female patients who are lactating should discontinue
             nursing prior to the first dose of study drug and should refrain from nursing
             throughout the treatment period and for 14 days following the last dose of study drug.