Sorafenib Dose Escalation in Renal Cell Carcinoma
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Sorafenib (Nexavar, BAY43-9006)
Intervention description: The initial dose of sorafenib will be 400 mg bid administered orally, on a continuous basis. A treatment cycle is considered to be 28 days. Intrapatient dose escalation will occur according to the following schedule, providing no grade 3 or 4 toxicities are observed (except for alopecia, nausea and vomiting); Day 1-28 400 mg bid, Day 29-56 600 mg bid, Day 57 onwards 800 mg bid. Subjects will continue on treatment until progression, unacceptable toxicity, subject withdraws consent or the decision is taken to stop the study following the analysis of response rates.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney cancer,; Sorafenib,; Dose escalation,; No previous treatment

Summary:

      Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of
      advanced kidney cancer. It is also currently being tested in various other cancers. Sorafenib
      works by stopping the development of new cancer cells and new blood vessels. By stopping the
      growth of new blood vessels around a tumor, it is believed that sorafenib prevents the growth
      of kidney cancer tumors.

      This is an "open-label" study which means that the patient, the doctor and Bayer Healthcare
      will know what tablets the patient is taking. All patients in this study will receive
      sorafenib tablets. Sorafenib is taken orally as a tablet (two tablets are taken twice a day).
      Treatment with sorafenib will continue until the patient's tumor grows larger or spreads
      further or if the patient has intolerable side effects. The dose of sorafenib that the
      patient will receive in the study will increase at certain points during the patient's
      treatment, as long as the patient is not experiencing side effects and the patient's tumor
      has not grown.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age > 18 years.

          -  Metastatic clear cell RCC (renal cell carcinoma)

          -  Subjects with at least one uni-dimensional measurable lesion.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category

          -  Life expectancy of at least 12 weeks.

          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory
             requirements to be conducted within 7 days prior to treatment

          -  Signed informed consent must be obtained prior to any study specific procedures.

          -  Subjects must have received no prior systemic anticancer therapy for the treatment of
             their renal cell carcinoma

          -  Prior total nephrectomy

        Exclusion Criteria:

          -  History of cardiac disease

          -  History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C

          -  Active clinically serious infections (> grade 2 National Cancer Institute-Common
             Terminology Criteria for Adverse Events [NCI-CTCAE] version 3.0)

          -  Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from
             definitive therapy, has a negative imaging study within 4 weeks of study entry and is
             clinically stable with respect to the tumor at the time of study entry.

          -  Subjects with evidence or history of bleeding diathesis

          -  Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of
             treatment.

          -  Delayed healing of wounds, ulcers or bone fractures

          -  Subjects with pre-existing thyroid abnormality whose thyroid function cannot be
             maintained within the normal range by medication

          -  Subjects undergoing renal dialysis

          -  Pregnant or breast-feeding subjects. Women of childbearing potential must have a
             negative serum pregnancy test performed within 7 days prior to the start of treatment.
             Both men and women enrolled in this trial must use adequate barrier birth control
             measures during the course of the trial and three months after the completion of
             trial.

          -  Prior adjuvant sorafenib is excluded.

          -  Radiotherapy during study or within 3 weeks of start of study drug

          -  Major surgery within 4 weeks of start of study

          -  Investigational drug therapy outside of this trial during or within 4 weeks of study
             entry