Phase I/II Trial of Anti-IGF-IR Monoclonal Antibody IMC-A12 Plus mTOR Inhibitor Temsirolimus (CCI-779) in Metastatic Castration-Resistant Prostate Cancer (CRPC)

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate

- Distant metastases evaluable by radionuclide bone scan, CT scan, or magnetic
resonance imaging (MRI) within the past 28 days

- Evidence of progressive disease during androgen-deprivation therapy (including a
trial of antiandrogen-withdrawal therapy), as defined by ≥ 1 of the following
criteria:

- Progressive measurable disease using conventional solid tumor criteria

- Bone scan progression, defined as ≥ 2 new lesions on bone scan

- Increasing PSA, defined as ≥ 2 consecutive rising PSA values over a reference
value taken ≥ 1 week apart (the third PSA value must be greater than the second
PSA value, if not, a fourth PSA value must be greater than the second PSA value)

- Castrate levels of serum testosterone (i.e., ≤ 50 ng/dL)

- No known brain metastases

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS
70-100%

- Life expectancy > 6 months

- Leukocytes ≥ 3,000/μL

- Absolute neutrophil count (ANC) ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 2 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN

- Serum creatinine ≤ 1.5 times ULN

- Creatinine clearance ≥ 50 mL/min

- Able to adhere to the study visit schedule and other study requirements

- Fertile patients must use effective contraception before, during, and for 3 months
after completion of study treatment

- Adequate lung function (pulmonary function test ≥ 70% for diffusion capacity of the
lung for carbon monoxide [DLco])

- No poorly controlled diabetes mellitus

- Patients with a history of diabetes are eligible provided their blood glucose is
normal (i.e., fasting blood glucose < 120 mg/dL or < ULN) and they are on a
stable dietary or therapeutic regimen

- No other malignancy within the past 3 years except for treated basal cell or squamous
cell carcinoma of the skin or superficial transitional cell carcinoma of the bladder

- No uncontrolled major illness including, but not limited to, any of the following:

- Active infection, including human immunodeficiency virus (HIV) infection or
viral hepatitis

- Symptomatic congestive heart failure (class III or IV)

- Unstable angina pectoris

- Myocardial infarction or acute coronary syndrome within the past year

- Serious cardiac arrhythmia

- Significant lung disease

- Major psychiatric illness

- No other concurrent anticancer agents or treatments

- No prior chemotherapy, except for neoadjuvant chemotherapy

- No prior anti-insulin-like growth factor receptor (IGFR) agents or mammalian target
of rapamycin (mTOR) inhibitors

- No prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionucleotide
therapy

- Prior standard-dose radiotherapy to the pelvis for prostate cancer and/or additional
external-beam radiotherapy to metastatic sites allowed

- More than 4 weeks since prior surgery, radiotherapy, combined androgen blockade
(excluding single-agent gonadotropin releasing-hormone agonists/antagonists), or
investigational therapies

- No concurrent second-line hormonal agents, including ketoconazole,
diethylstilbestrol, other estrogen-like agents, or finasteride

- No concurrent corticosteroids unless patient is on a stable maintenance dose of
hydrocortisone (≤ 30 mg/day) for ≥ 3 months