Sorafenib and Docetaxel in Patients With Prostate Cancer That Did Not Respond to Previous Hormone Therapy
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: docetaxel; sorafenib tosylate
Intervention MeSH terms: Docetaxel; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Male
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer

Summary:

      RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways
      to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving sorafenib together with docetaxel may kill more tumor cells.

      PURPOSE: This phase II trial is studying giving sorafenib together with docetaxel to see how
      well it works in treating patients with metastatic androgen-independent prostate cancer.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate with clinical
             or radiological evidence of metastatic disease.

          -  Serum PSA >5 ng/mL.

          -  Patients must have discontinued flutamide or nilutamide for at least 4 weeks and
             bicalutamide for at least 6 weeks

          -  Disease progression during hormonal therapy defined as at least one of the following:

               1. increasing serum PSA levels on at least two measurements at least two weeks
                  apart.

               2. Progressive measurable disease (by RECIST criteria) independent of PSA

               3. Bone scan progression with at least one new lesion.

          -  Serum testosterone ≤ 50 ng/dL. Patients must be receiving primary androgen ablation
             therapy with a GnRH agonist as maintenance therapy unless surgically castrated.

          -  Age > 18 years.

          -  ECOG performance status of ≤ 1.

          -  Baseline laboratory values (evaluated within 14 days of randomization):

        White Blood Count > 3,000/mm3 Absolute Granulocyte Count > 1,500/mm3 Platelet Count >
        100,000/mm3 Serum creatinine < 2.0 x upper limit of normal (ULN) INR < 1.5 before the start
        of chronic anticoagulation and a PTT within normal limits

          -  Liver Function Total Bilirubin less or equal to ULN AST and ALT must be <5X ULN for
             eligibility. In determining eligibility the more abnormal of the two values (AST or
             ALT) should be used.

          -  Prior radiation therapy is allowed. However, if radiation has been administered to a
             lesion, there must be radiographic evidence of progression of that lesion in order for
             that lesion to constitute measurable disease or to be included in the measured target
             lesions. 4 weeks must have elapsed between radiation therapy and entry into study.

          -  Prior vaccine therapy is allowed

          -  Prior and/or concurrent zoledronic acid (Zometa) therapy is allowed.

          -  Men of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter.

        Exclusion criteria:

          -  Prior therapy with cytotoxic chemotherapy

          -  Prior therapy with radioisotopes

          -  History of brain metastasis or leptomeningeal disease

          -  Symptomatic neuropathy >grade2

          -  Prior history of cancer (except basal cell or squamous-cell skin cancer) within the
             past 5 years (exceptions must be approved by the PI)

          -  Prior history of DVT or Pulmonary embolism in the last 1 year

          -  Patients must not have a serious medical illness including, but not limited to,
             ongoing or active infection requiring parental antibiotics; clinically significant
             cardiovascular disease (e.g. uncontrolled hypertension, recent myocardial infarction,
             unstable angina), New York heart association grade II or greater congestive heart
             failure, or grade II or greater peripheral arterial vascular within 1 year prior to
             study entry, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs
             (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort.

          -  Patients must not be taking drugs that inhibit CYP3A at the time of enrollment to
             prevent drug-drug interactions with docetaxel. These include ketoconazole,
             voriconazole, itraconazole, fluconazole, cimetidine, clarithromycin, erythromycin,
             troleandomycin, and grapefruit juice. These agents should be avoided during treatment
             while on study.

          -  Because patients with immune deficiency are at increased risk of lethal infections
             when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded
             from the study. For patients receiving combination anti-retroviral therapy, the
             potential impact of pharmacokinetic interactions with sorafenib and docetaxel is
             unknown. Appropriate studies may be undertaken in patients with HIV and those
             receiving combination anti-retroviral therapy in the future.

          -  Patients with a history of severe hypersensitivity reaction to docetaxel or other
             drugs formulated with polysorbate 80