Phase 2 Single Arm, Open-Label Study of IMC-A12 in Asymptomatic, Chemotherapy-Naïve Patients With Metastatic Androgen-Independent Prostate Cancer

Inclusion Criteria

Inclusion Criteria

- The patient is male and at least 18 years of age

- The patient has histologically-confirmed adenocarcinoma of the prostate

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

- The patient has prostate cancer unresponsive or refractory to hormone therapy

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

- a. Progressive measurable disease: using conventional solid tumor criteria.

- b. Bone scan progression: at least one new lesion on bone scan.

- c. 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 not received prior chemotherapy for metastatic prostate cancer

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

- All clinically significant toxic effects (excluding alopecia) of prior surgery,
radiotherapy, or hormonal therapy have resolved to grade ≤ 1 based on National Cancer
Institute - Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE)

- The patient has not received antiandrogen therapy for at least 6 weeks (4 weeks for
flutamide) prior to study entry and is without evidence of an antiandrogen withdrawal
response. For patients whose progression is documented solely by PSA increase, the
most recent PSA value enabling study entry must be drawn after the required
antiandrogen washout period

- The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of
0-1

- The patient has adequate organ function including: absolute neutrophil count ≥
1500/μL; platelets ≥ 100,000/μL; hemoglobin ≥ 9.0 g/dL; bilirubin ≤ 1.5 times the
institutional upper limit of normal (ULN); aspartate transaminase (AST)/alanine
transaminase (ALT) ≤ 3 times ULN (< 5x ULN if liver metastases are present);
creatinine ≤ 1.5 x ULN (or calculated creatinine clearance > 60 mL/min); and urine
protein ≤ 1+ (if urine protein is ≥ 2+, a 24-hour urine collection must demonstrate <
1000 mg of protein in 24 hours to allow participation in the study)

- The patient has fasting serum glucose < 120 mg/dL or below the ULN

- The patient has adequate coagulation function as defined by an international
normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 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 is asymptomatic from prostate cancer. Patients with minimal, infrequent
cancer-related symptoms are eligible. Criteria regarding pain and analgesic use are
detailed below

- The patient has a life expectancy > 6 months

- The patient, if sexually active, agrees to use contraceptives while on study

- The patient has provided signed informed consent

Exclusion Criteria

- The patient has any active malignancy (other than adequately treated nonmelanomatous
skin cancer or other noninvasive or in situ neoplasms), or has an adequately-treated
prior cancer but has been disease free for < 3 years

- The patient has an ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, serious cardiac arrhythmia (well-controlled atrial
fibrillation is permitted), psychiatric illness/social situations, active bleeding or
pathological condition that carries a high risk of bleeding (eg, tumor involving
major vessels, tumor invading to rectal lumen, or known varices), or any other
serious uncontrolled medical disorder in the opinion of the investigator

- The patient has a known hypersensitivity to therapeutic protein products

- The patient has known or suspected brain or leptomeningeal metastases

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

- The patient has received prior radiation therapy to > 30% of the bone marrow or prior
strontium-89, rhenium-186, rhenium-188, or samarium-153 (patients who have received
standard dose radiation to the pelvis for prostate cancer and no additional
radiotherapy are eligible)

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

- The patient has received more than one course of radiotherapy to a single site of
metastatic bony disease

- The patient has a bone scan that indicates "superscan" (ie, extensive metastasis to
bone in numerous areas, too numerous to count or define)

- The patient is receiving corticosteroids (dexamethasone, prednisone, or others) for
anorexia, weight loss, analgesia or other cancer-related symptoms(Corticosteroids may
not be instituted once a patient has begun therapy on-study

- The patient requires ongoing, regularly scheduled opiate analgesic therapy for cancer
related pain. Intermittent, infrequent low-potency opiate-use (eg, oxycodone,
codeine) is permitted

- The patient has a history of prior treatment with other agents that specifically
target the IGF receptor