Everolimus Post Pazopanib Treatment in Metastatic or Advanced Renal Cell Carcinoma
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Pazopanib followed by everolimus
Intervention description: All patients received Pazopanib (800 mg once daily orally continuous dosing) until disease progression then second line everolimus (10 mg once daily orally continuous dosing)
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Renal cell carcinoma (RCC), GW786034, Everolimus, Pazopanib, renal cancer, cancer, kidney cancer, hypernephroma, Grawitz tumor, renal adenocarcinoma.

Summary:

      Study to determine the efficacy, safety and tolerability of first-line pazopanib followed by
      second-line everolimus in metastatic and advanced renal cell carcinoma.

      Due to changes in the RCC treatment landscape, info gained is no longer clinically relevant
      to patients. Data collected is deemed sufficient to meet objective.
    

Eligibility criteria:

        Inclusion criteria:

          -  Age >=18 years

          -  Histologically confirmed RCC with a clear-cell component

          -  Locally advanced or metastatic RCC

          -  At least one measurable lesion per RECIST 1.1 criteria, as determined by Computer
             Tomography (CT) Scan or Magnetic Resonance Imaging (MRI)

          -  No systemic therapy for advanced or metastatic RCC prior to enrollment

          -  Karnofsky Performance Status (KPS) ≥70

          -  Adequate baseline organ function

          -  A female was eligible to enter and participate in this study if she was of:
             non-childbearing potential, or negative serum pregnancy test with agreement to use
             adequate contraception during the study

          -  A male with female partner of childbearing potential must have vasectomy/agree to use
             effective contraception from 2 weeks prior to administration of the 1st dose of study
             treatment for a period of time after the last dose of study treatment

          -  Able to swallow and retain orally administered medication and must not have clinically
             significant GI abnormalities that may alter absorption

        Additional inclusion criteria for starting everolimus:

          -  Disease progression must be within 6 months after stopping pazopanib

          -  At least one measurable lesion at the start of everolimus pe r RECIST 1.1 criteria, as
             determined by CT or MRI

          -  In case of central nervous system (CNS) progression or metastasis during pazopanib
             treatment: asymptomatic or neurologically stable, no requirement of steroids to
             control CNS symptoms, and no requirement of enzyme-inducing anticonvulsants within 4
             weeks prior to the start of everolimus

        Exclusion Criteria:

          -  Lactating female

          -  History of another malignancy (exception: patients disease-free for ≥3 years and
             patients with completely resected non-melanoma skin cancer or successfully treated in
             situ carcinoma)

          -  Symptomatic CNS metastases at baseline

          -  Clinically significant gastrointestinal abnormalities

          -  Moderate to severe hepatic impairment (Child Pugh Class C)

          -  Receiving chronic treatment with corticosteroids/other immunosuppressive agents

          -  Active bleeding, bleeding diathesis or on oral anti-vitamin K medication (except low
             dose coumadin)

          -  Corrected QT interval (QTc) >480 msec using Bazett's formula

          -  Presence of any severe or uncontrolled medical conditions/infection

          -  Poorly controlled hypertension (defined as systolic blood pressure of >=140mmHg or
             diastolic blood pressure of >=90mmHg)

          -  History of cardiovascular disorders within the last 12 months (e.g. myocardial
             infraction or unstable angina), history of cerebrovascular events or pulmonary
             embolism within the last 6 months

          -  Active bleeding or bleeding susceptibility

          -  Known endobronchial lesion and/or lesions infiltrating major pulmonary vessels that
             increased the risk of pulmonary hemorrhage

        Additional criteria for exclusion from the second-line everolimus treatment period:

        - The subject felt by the investigator to be unsuitable (on the basis of health,
        compliance, or for any other reason) for inclusion in the study.