Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer
Study With IMC-A12 (Cixutumumab) in Patients Who Have Not Previously Been Treated With Chemotherapy With Metastatic Prostate Cancer
This single arm, multicenter, open-label, Phase II study will enroll chemotherapy-naive
 participants with metastatic, histologically-confirmed adenocarcinoma of the prostate (stage
 M1 D2). Treatment will continue until there is evidence of disease progression, intolerable
 toxicity, or other withdrawal criteria are met. Non-surgically castrated participants must
 continue the use of luteinizing hormone-releasing hormone (LHRH) agonists during protocol
 treatment.
Thirty-one chemotherapy-naїve participants with asymptomatic metastatic androgen-independent
 prostate cancer will be enrolled and treated with intravenous (i.v.) IMC-A12 (Cixutumumab) at
 10 milligrams per kilogram (mg/kg) administered over 1 hour every 2 weeks. An additional 10
 participants will be enrolled and treated with IMC-A12 at a dose of 20 mg/kg every three
 weeks. Treatment will continue until evidence of disease progression or intolerable toxicity.
 Radiographic evaluation of response will be performed every 8 weeks for the participants
 treated with i.v. IMC-A12 at 20 mg/kg.
Inclusion Criteria

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

 -  The participant has histologically-confirmed adenocarcinoma of the prostate

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

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

 -  The participant 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 prostate specific antigen (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 participant has a PSA ≥ 2 nanograms/milliliter (ng/mL)

 -  The participant has not received prior chemotherapy for metastatic prostate cancer

 -  The participant had prior surgical or medical castration with a serum testosterone
 level of < 50 ng/mL. If the method of castration is LHRH agonists, the participant
 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, (NCI-CTCAE)Version 3.0

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

 -  The participant has adequate organ function including: absolute neutrophil count ≥
 1500/microliter (μL); platelets ≥ 100,000/μL; hemoglobin ≥ 9.0 grams per deciliter
 (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 milliliter/minute (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 participant has fasting serum glucose < 120 milligrams per deciliter (mg/dL) or
 below the ULN

 -  The participant 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). Participants 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 participant is asymptomatic from prostate cancer. Participants with minimal,
 infrequent cancer-related symptoms are eligible. Criteria regarding pain and analgesic
 use are detailed below

 -  The participant has a life expectancy > 6 months

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

 -  The participant has provided signed informed consent

 Exclusion Criteria

 -  The participant 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 participant 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 participant has a known hypersensitivity to therapeutic protein products

 -  The participant has known or suspected brain or leptomeningeal metastases

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

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

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

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

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

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

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

 -  The participant has a history of prior treatment with other agents that specifically
 target the insulin-like growth factor (IGF) receptor