Mitoxantrone ± Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC)

This is a nonblinded, randomized phase II study to determine the activity of Novantrone (mitoxantrone) with or without Erbitux (cetuximab) in patients with androgen independent prostate cancer (AIPC) who have been treated previously with docetaxel chemotherapy. The Novantrone (mitoxantrone)-only treatment arm will serve as a concurrent control arm to aid in the determination of the benefit of the Novantrone (mitoxantrone)-Erbitux (cetuximab) combination in this setting.

Patients will be randomly assigned 2:1 to 1 of 2 treatment arms; 93 patients in Arm 1 and 47 patients in Arm 2. A balanced randomization procedure will be performed utilizing a code list that will be developed prior to the study opening. Because the patients will be stratified by performance status (ECOG 0 and 1 vs. ECOG 2), the list will be developed to ensure a balance between the 2 treatment arms.

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