A Phase 2, Multicenter, Randomized Study of IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer (AIPC) Following Disease Progression on Docetaxel-Based Chemotherapy

Inclusion Criteria:

- The patient has histologically-confirmed adenocarcinoma of the prostate

- The patient has radiographic evidence of metastatic prostate cancer (stage M1 or D2)

- The patient has prostate cancer unresponsive or refractory to hormone therapy
(androgen-independent)

- The patient has had disease progression (clinical or radiographic) while receiving
docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the
opinion of the investigator is unlikely to derive significant benefit from additional
docetaxel-based therapy, or was intolerant to therapy with this agent

- The patient must have evidence of progressive disease defined as at least one of the
following;

1. Progressive measurable disease: using conventional solid tumor criteria

2. Bone scan progression: at least two new lesions on bone scan

3. Increasing PSA: at least two consecutive rising PSA values over a reference
value (PSA #1) taken at least 1 week apart. 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

- The patient has a PSA ≥ 2 ng/mL

- The patient has prior surgical or medical castration with a serum testosterone of <50
ng/mL. If the method of castration is luteinizing hormone releasing level hormone
(LHRH) agonists, the patient must be willing to continue the use of LHRH agonists
during protocol treatment

- The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS)
0-2

- The patient has adequate hematologic function (absolute neutrophil count
[ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

- The patient has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of
normal (ULN)], aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times
the ULN, or ≤ 5 times the ULN if liver metastases are present)

- The patient has adequate renal function (creatinine ≤ 1.5 x ULN or calculated
creatinine clearance > 40 mL/min)

- The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If
urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine
must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow
participation in the study

- The patient has adequate coagulation function (an international normalized ratio
[INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless
on oral anticoagulant therapy]). Patients receiving full-dose anticoagulation therapy
are eligible provided they meet all other criteria, are on a stable dose of oral
anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic
INR between 2 and 3)

- The patient has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

- The patient has received more than one prior cytotoxic chemotherapy regimen for
metastatic disease. (Patients who have had a treatment break followed by a second
docetaxel-based regimen with subsequent disease progression are eligible.)

- The patient has received prior therapy with mitoxantrone for advanced prostate cancer
(prior adjuvant therapy with mitoxantrone is permitted)

- The patient has a history of symptomatic congestive heart failure or has a pre-study
echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection
fraction (LVEF) that is ≥ 10% below the LLN

- The patient has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or
Ramucirumab

- The patient is receiving corticosteroids (dexamethasone, prednisone, or others) at a
dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Patients
receiving corticosteroids at higher doses may be eligible if their corticosteroid
therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of
study medication, without concomitant clinical deterioration

- The patient has known or suspected brain or leptomeningeal metastases

- The patient has uncontrolled or poorly controlled hypertension

- The patient has poorly controlled diabetes mellitus. Patients with a history of
diabetes are allowed to participate, provided that their blood glucose is within
normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary
or therapeutic regimen for this condition

- The patient has a known human immunodeficiency virus infection or acquired
immunodeficiency syndrome-related illness