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A Phase II Study of Sorafenib in Combination With Docetaxel in Patients With Androgen-Independent Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

A Phase II Study of Sorafenib in Combination With Docetaxel in Patients With 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.

Inclusion Criteria


- 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


- 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:

- Ketoconazole

- Voriconazole

- Itraconazole

- Fluconazole

- Cimetidine

- Clarithromycin

- Erythromycin

- Troleandomycin

- Grapefruit juice

- No concurrent combination antiretroviral therapy for HIV-positive patients

- Concurrent bisphosphonate therapy allowed

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PSA response rate

Safety Issue:


Principal Investigator

Amy Kramer, RN, MPA

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania



Study ID:




Start Date:

October 2006

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • Prostatic Neoplasms



Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283