Mitoxantrone ± Cetuximab 2nd Line Androgen Independent Prostate Cancer (AIPC)
Condition: Androgen-independent Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: cetuximab; Mitoxantrone
Intervention description: Erbitux (cetuximab) IV over 2 hours (loading dose) on Day 1 (Cycle 1 only), followed by Erbitux (cetuximab) IV over 1 hour weekly thereafter; Novantrone (mitoxantrone) IV Day 1 + Prednisone QD for ten (10) 21-day cycles Standard androgen deprivation therapy (ADT) will be continued in all patients who enter study on LHRH agonists
Intervention MeSH terms: Cetuximab; Mitoxantrone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Androgen-independent prostate cancer(AIPC)

Summary:

      To determine the time to progression produced by the combination of Novantrone (mitoxantrone)
      and Erbitux (cetuximab) versus Novantrone alone in metastatic AIPC patients previously
      treated with docetaxel-based chemotherapy. TTP is defined as time from the start of treatment
      date to the date the patient is first recorded as having disease progression, even in
      patients who discontinue study treatment early due to toxicity.
    

Eligibility criteria:

        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