A Randomized Phase II Study of Mitoxantrone vs. Mitoxantrone With Cetuximab in Metastatic Androgen Independent Prostate Cancer (AIPC) Previously Treated With Docetaxel-based Chemotherapy

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate. Note: Patients may have
either measurable or non-measurable disease.

- Radiographic evidence of regional or distant metastases

- Current evidence of progression (by PSA and/or imaging studies) despite standard
hormonal therapy.

- Progression by PSA will be defined as: A rising PSA defined as: at least 2 rises in
PSA over a reference value (PSA #1). The first rising PSA (PSA #2) must be taken at
least 1 week after PSA #1. A third PSA (PSA #3) is required to be greater than PSA
#2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2. Progression
for nonmeasurable disease will be defined as 2 or more new bone lesions; for
measurable disease, progression will be defined by standard RECIST criteria.

- For patients who have been on antiandrogen therapy (ie, bicalutamide, flutamide,
etc.), patients must have discontinued anti-androgen therapy for at least 6 weeks (4
weeks for flutamide) without evidence of an antiandrogen withdrawal response. A
washout period will not be required for patients who did not respond to an
antiandrogen prescribed as second line hormonal therapy. For patients whose
progression is documented by PSA, the last required PSA must be after the required
anti-androgen washout period (4-6 weeks as appropriate).

- One prior docetaxel-containing regimen. Patients must have received at least 2 doses
in an every 3-week schedule or 6 doses on a weekly schedule of docetaxel. Patients
may have discontinued therapy due to progression, intolerance, completion of planned
therapy, or other reasons. Chemotherapy treatment with any second-line regimen will
not be permitted. Patients who have been previously treated with a first-line
docetaxel-based doublet regimen will be eligible for this study, (eg, patients
treated on a prior first-line trial containing a docetaxel/carboplatin or other
docetaxel-based doublet).

- Serum testosterone levels (See protocol for specific details) (unless surgically
castrate). Patients must continue androgen deprivation with an LHRH agonist if they
have not undergone orchiectomy

- ECOG performance status

- Laboratory criteria for entry:

- absolute neutrophil count

- platelets

- bilirubin

- AST or ALT

- Life expectancy greater than 3 months

- Age greater than or equal to 18 years

- Agree to use contraceptives while on study if sexually active, and for 2 months after
the last dose of study drug.

- Has signed a Patient Informed Consent Form

- Has signed a Patient Authorization Form

Exclusion Criteria:

- More than 1 prior chemotherapy regimen for metastatic disease

- Prior history of uncontrolled congestive heart failure or left ventricular ejection
fraction (LVEF) that is less than the institution's lower limit of normal on MUGA or
echocardiogram

- A second active malignancy (diagnosed within 5 years) except adequately treated
non-melanoma skin cancer or other non-invasive or in-situ neoplasm

- Significant active concurrent medical illness or infection

- Treatment with chemotherapy for AIPC within the past 21 days

- Prior treatment with Novantrone (mitoxantrone)

- Prior therapy which specifically and directly targets the EGFR pathway

- Prior severe infusion reaction to a monoclonal antibody

- Recent myocardial infarction (within prior 6 months)

- Prior treatment with radionuclides, with the exception of prior treatment with
samarium, which will be allowed provided at least 8 weeks have passed since
administration.

- Is receiving concurrent immunotherapy, hormonal therapy, radiation therapy, or any
other non-protocol therapy (excluding LHRH antagonist)

- Is receiving concurrent investigational therapy or has received such therapy within
the past 30 days

- Has evidence of CNS involvement

- Has a serious uncontrolled intercurrent medical or psychiatric illness, including
serious infection.

- Is unable to comply with requirements of study