Study of Irofulven in Patients With Hormone-refractory Prostate Cancer

For every five patients randomized, two will receive treatment number 1 (irofulven +
prednisone), two patients will receive treatment number 2 (irofulven + capecitabine
(Xeloda®) + prednisone), and one patient will receive treatment number 3 (mitoxantrone +
prednisone). This is not a blinded study, so both the patient and doctor will know which
treatment has been assigned.

Inclusion Criteria:

To be included in the study, patients must meet the following criteria:

1. Cancer of the prostate confirmed by a biopsy sample.

2. 18 years of age or older.

3. Disease must have spread beyond the prostate as proven by chest x ray, abdominal and
pelvic computed tomography (CT) scan, bone scan or clinical examination.

4. At least one prior hormonal treatment with documented disease progression during
hormone therapy.

5. One previous line of chemotherapy that included Taxotere® (as monotherapy or in
combination). This could be in addition to estramustine single agent therapy.

6. Disease progression during prior Taxotere-based therapy or within 3 months of
discontinuing.

7. Recovered from any toxic effects of prior chemotherapy, radiotherapy and surgery.

8. Recovered from any toxic effects associated with other investigational drugs, if
applicable.

9. Signed informed consent obtained prior to initiation of any study-specific procedures
or treatment.

Exclusion Criteria:

Patients cannot participate in the study if any of the following apply:

1. Unable to use prednisone.

2. Prior treatment with irofulven, capecitabine (Xeloda), continuous/protracted infusion
5-FU (5-fluorouracil) (infusion duration greater than or equal to 24 hours), other
fluoropyrimidines or mitoxantrone.

3. Ongoing treatment with a corticosteroid at a prednisone-equivalent dose > 10 mg/day.

4. More than 1 prior treatment with either 153Sm or 89Sr, or radioisotope treatment
within 8 weeks prior to entering this study.

5. Initiation of treatment with bisphosphonate agents (e.g., pamidronate, etidronate)
within 2 months of entering the study. Pre-existing treatment with bisphosphonate
agents is to be continued during this study.

6. Treatment with warfarin and/or phenytoin within 14 days before entering this study or
during the study period.

Please note: There are additional inclusion/exclusion criteria. The study center will
determine if patients meet all of the criteria. If patients do not qualify for the trial,
study personnel will explain the reasons. If patients do qualify, study personnel will
explain the trial in detail and answer any questions. Patients can then decide if they
wish to participate.