Evaluate Safety and Tolerability in Dose Escalation of Sorafenib in Advanced Renal Cell Cancer
Condition: Renal Cell Cancer
MeSH terms: Carcinoma, Renal Cell
Intervention: sorafenib
Intervention description: Dose Level:
400mg twice daily, continuous.
600mg twice daily, days 1-5 of each week.
800mg twice daily, days 1-5 of each week.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: carcinoma, renal cell; kidney; cancer

Summary:

      The purpose of this study is to determine whether an increase in the dose of sorafenib when
      given over five instead of 7 days/week, will result in an improvement of the response rate
      (degree of shrinkage of your cancer) and an improvement in the length of time that sorafenib
      will control your cancer, without causing a significant increase in side effects.
    

Eligibility criteria:

        Inclusion Criteria

          -  Age ≥ 18 years old.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

          -  Adequate bone marrow, liver and renal function as assessed by the following:

               -  Hemoglobin ≥ 9.0 grams per deciliter (g/dl)

               -  Absolute neutrophil count (ANC)≥ 1,500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

               -  and aspartate aminotransferase (AST) ≤ 2.5 times the ULN (≤ 5 x ULN for patients
                  with liver involvement)

               -  Creatinine < 1.5 times ULN

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to of treatment.

          -  Women of childbearing potential and men must agree to use adequate contraception
             (barrier method of birth control) prior to study entry and for the duration of study.
             Men should use adequate birth control for at least three months after the last
             administration of sorafenib.

          -  Ability to understand and willing to sign written informed consent. A signed informed
             consent must be obtained prior to any study specific procedures.

          -  International normalized ratio (INR) < 1.5 or a prothrombin time/partial prothrombin
             time (PT/PTT) within normal limits unless receiving anti-coagulation treatment with an
             agent such as warfarin or heparin. These patients may be allowed to participate. For
             patients on warfarin, the INR should be measured prior to initiation of sorafenib and
             monitored at least weekly, or as defined by the local standard of care, until INR is
             stable.

          -  Must have histologically or cytologically confirmed renal cell carcinoma that is
             metastatic (M1). Patients with unresectable primary tumor (but MO) are also eligible.

          -  Must have measurable disease, defined as at least 1 lesion that can be accurately
             measured in at least 1 dimension. Soft tissue disease that has been radiated in the 2
             months prior to registration is not assessable as measurable disease. Soft tissue
             disease within a prior radiation field must have progressed to be considered
             assessable. X-rays, scans or physical examinations used for tumor measurement must
             have been completed within 28 days prior to registration. X-rays, scans or physical
             examinations for non-measurable disease must have been completed within 42 days prior
             to registration.

          -  Patients with metastatic disease who have a resectable primary tumor and are deemed a
             surgical candidate may have undergone resection and have recovered from surgery. At
             least 28 days must have elapsed since surgery and must have recovered from any adverse
             effects of surgery.

          -  May have received 1 prior immunotherapy with either interferon (IFN) and/or
             Interleukin-2 (IL-2) or the combination of IFN/IL2 and only 1 prior biologic agent
             (sunitinib, bevacizumab, or temsorlimus). Must have progressed during this prior
             therapy. At least 14 days must have elapsed since the last treatment and must have
             recovered from any adverse effects of prior therapy. May have received prior radiation
             therapy. At least 21 days must have elapsed since completion of prior radiation
             therapy. Must have recovered from all associated toxicities at the time of
             registration.

        Exclusion Criteria

          -  Cardiac disease: Congestive heart failure > class II New York Heart Association
             (NYHA). Must not have unstable angina (anginal symptoms at rest) or new onset angina
             (began within the last 3 months) or myocardial infarction within past 6 months.

          -  Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI
             of the brain to exclude brain metastasis.

          -  Patients who have received prior sorafenib are ineligible.

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
             pressure > 90 mmHg, despite optimal medical management.

          -  Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B/C.

          -  Active clinically serious infection > CTCAE Grade 2.

          -  Thrombosis or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months. Patients with renal or caval thrombosis
             related to the primary renal tumor would not be excluded and are eligible.

          -  Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of
             study drug.

          -  Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of
             study drug.

          -  Serious non-healing wound, ulcer, or bone fracture.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
             study drug.

          -  Use of St. John's Wort or rifampin (rifampicin).

          -  Known or suspected allergy to sorafenib or any agent given in the course of this
             trial.

          -  Any condition that impairs patient's ability to swallow whole pills.

          -  Any malabsorption problem.