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.
- To determine the proportion of patients achieving a 50% reduction in serum PSA from
baseline in patients with androgen-independent prostate cancer (AIPC) receiving
sorafenib tosylate and docetaxel.
- To estimate the progression-free survival of patients with AIPC.
- To quantify the number and percent of patients who have stable disease at 6 months of
therapy (failure to progress).
- To estimate median time to progression for all patients.
- To estimate the objective response rate of patients with AIPC treated with this
- To measure the percentage of patients surviving at 2 years.
- To determine the toxicities and estimate toxicity rates for patients treated with this
- To measure changes in tumor vasculature in response to therapy in selected patients
with dynamic contrast-enhanced MRI (DCE-MRI) and correlate primary and secondary
objectives to these measurement changes.
- To measure changes in serum HMGB1 in response to therapy and correlate primary and
secondary objectives with these changes.
- To measure changes in serum cathepsin D in response to therapy and correlate primary
and secondary objectives with these changes.
OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 2-19 and docetaxel IV
on day 1. Treatment repeats every 21 days for up to 10 courses. Patients then receive oral
sorafenib tosylate alone twice daily on days 1-19 with treatment repeating every 21 days in
the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically to measure serum HMGB1 and cathepsin D levels
before and after therapy.
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Androgen-independent disease
- Metastatic disease measured by clinical or radiological evidence
- Disease progression during hormonal therapy, defined by one or more of the following:
- Increasing serum PSA levels on ≥ 2 measurements at least two weeks apart
- Progressive measurable disease (by RECIST criteria) independent of PSA
- Bone scan progression with at least one new lesion
- Must be receiving primary androgen ablation therapy with gonadotropin-releasing
hormone agonists (GnRH) as maintenance therapy unless surgically castrated
- Serum PSA > 5 ng/mL
- No history of brain metastasis or leptomeningeal disease
- ECOG performance status 0-1
- WBC ≥ 3,000/mm³
- Absolute granulocyte count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 2.0 times the upper limit of normal (ULN)
- Total bilirubin normal
- AST and ALT ≤ 5 times ULN
- INR ≤ 1.5 and PTT normal (before the start of chronic anticoagulation)
- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study therapy
- No symptomatic neuropathy grade ≥ 2
- No HIV positivity
- No history of cancer except basal cell or squamous-cell skin cancer within the past 5
- No history of deep vein thrombosis or pulmonary embolism within the past year
- No serious medical illness including, but not limited to, any of the following:
- Ongoing or active infection requiring parental antibiotics
- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension,
recent myocardial infarction, unstable angina)
- NYHA class II-IV congestive heart failure
- NYHA class II-IV peripheral arterial vascular disease within the past year
- Psychiatric illness or social situations that would limit study compliance
- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior flutamide or nilutamide (6 weeks for bicalutamide)
- At least 4 weeks since prior radiotherapy
- Must have radiographic evidence of progression of any lesion that has received
radiotherapy in order for that lesion to constitute measurable disease or be
considered a measured target lesion
- Prior vaccine therapy allowed
- Prior and/or concurrent zoledronic acid therapy allowed
- No prior cytotoxic chemotherapy
- No prior radioisotope therapy
- No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin,
carbamazepine, or phenobarbital)
- No concurrent rifampin or St. John's wort
- No concurrent inhibitors of CYP3A, including any of the following:
- Grapefruit juice
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Concurrent bisphosphonate therapy allowed