Study of SU11248 in Men With Advanced Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Sunitinib
Intervention description: Sunitinib 50 mg daily, 4/2 schedule
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sutent; Sunitinib; Bone; Metastatic; Hormone-refractory; Biomarkers

Summary:

      -  There are nearly 30,000 deaths per year in the United States from prostate cancer,
           making this a large and important target patient population for new cancer treatments.

        -  SU011248 is an exciting, new, experimental drug that inhibits a number of proteins, or
           more specifically receptor tyrosine kinases, in tumor cells. These proteins are active
           in cellular pathways that are important for development and growth of a variety of
           different cancers. The targets of SU011248 include the receptors for vascular
           endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and others. By
           blocking the VEGF and PDGF pathways, SU011248 can induce death of the blood vessels that
           nourish the cancer cells and death of the cancer cells themselves.

        -  SU011248 has demonstrated significant anti-tumor activity in renal cell carcinoma,
           gastrointestinal stromal tumors, and other cancers. Its effect against prostate cancer
           has not been studied to date.

        -  This study is directed at two populations of men with advanced prostate cancer:

             1. Men with advanced prostate cancer who have a rising PSA despite hormone therapy,
                but have not yet received any chemotherapy.

             2. Men with metastatic prostate cancer who have received prior chemotherapy (with a
                docetaxel-based regimen) and have increasing disease following chemotherapy.

        -  Men in this study will receive SU011248 on a six-week repeating schedule, with four
           weeks of daily treatment followed by a two-week rest. The goals of the study are:

             1. to determine whether SU011248 is an important therapeutic agent in men with
                advanced prostate cancer, and

             2. to identify predictive markers of anti-cancer activity within individual subjects
                that would allow selective treatment of appropriate subjects in the future.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent indicating that the subject has been informed of all pertinent
             aspects of the trial.

          -  Adenocarcinoma of the prostate

          -  Male subjects, 18 years of age or older

          -  Life expectancy of > 12 weeks

          -  Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical
             procedure to National Cancer Institute Common Toxicity Criteria Adverse Event (NCI
             CTCAE) grade <1

          -  Surgical or ongoing chemical castration

          -  Androgen-independent disease, defined as progressive disease despite surgical or
             ongoing chemical castration. See section 8.2.3 for definition of progressive disease.

          -  Eastern Cooperative Oncology Group performance status of 0, 1 or 2

          -  Adequate bone marrow reserve:

               -  Neutrophil count > 1,500/ul

               -  Platelet count > 75,000/ul

          -  Adequate hepatic function:

               -  Serum bilirubin < 1.5 x upper limit of normal

               -  Asparate aminotransferase and alanine aminotransferase < 2.5 x upper limit of
                  normal

          -  Adequate renal function, with serum creatinine < 2 x upper limit of normal

          -  Prostate Specific Antigen (PSA) > 5.0 ng/mL, based on PSA Working Group Criteria

          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests and other study procedures

        For Group A only:

        · No prior treatment for prostate cancer with cytotoxic chemotherapy

        For Group B only:

          -  Radiographic evidence of metastatic prostate cancer

          -  One prior docetaxel-based chemotherapy regimen, minimum of two cycles

          -  Disease progression during treatment with docetaxel, or within 60 days of receiving
             docetaxel

        Exclusion Criteria:

          -  Small cell carcinoma of the prostate

          -  Treatment with extensive external beam radiation therapy or radionuclide therapy
             within six weeks of study entry. Palliative radiation involving less than 20% of bone
             marrow reserves must have been completed within four weeks of entry.

          -  Any of the following within the prior 6 months: unstable angina, myocardial
             infarction, symptomatic congestive heart failure or cerebrovascular accident

          -  Receipt of any investigational anti-cancer agent within 4 weeks of the study

          -  NCI CTCAE grade 3 hemorrhage < 4 weeks of starting study treatment

          -  Uncontrolled hypertension

          -  Prolongation of the QTc interval to > 450 msec

          -  Other serious acute or chronic medical or psychiatric condition that may increase the
             risk associated with study participation, and in the judgment of the investigator
             would make the subject inappropriate for entry into this study.