RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may be a better way to block tumor growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with bevacizumab and to see how well it works in treating patients with hormone-resistant metastatic prostate cancer that did not respond to chemotherapy.

PRIMARY OBJECTIVES:

I. The primary objective of the Phase I portion of this study is to determine the maximum tolerated dose (MTD) of temsirolimus in combination with AVASTIN in subjects with chemotherapy refractory metastatic CRPC.

II. The primary objective for the Phase II portion of this study is to evaluate the objective response frequency (PSA and RECIST-Response Evaluation Criteria in Solid Tumors-defined) of the combination of temsirolimus and AVASTIN in patients with chemotherapy refractory metastatic CRPC.

SECONDARY OBJECTIVES:

I. To evaluate the effect of the combination of temsirolimus and AVASTIN on time to clinical progression and overall survival in patients with chemotherapy refractory metastatic CRPC.

II. To further evaluate the safety of temsirolimus given in combination with AVASTIN in chemotherapy refractory metastatic CRPC patients at the dose established in our phase I safety phase.

III. To determine the presence of circulating tumor cells (CTCs) and status of single nucleotide polymorphism (SNPs) in CRPC patients. (Exploratory)

OUTLINE: Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 28 days.

Inclusion

• Understand and voluntarily sign an informed consent form
• Patients with histologically confirmed adenocarcinoma of the prostate
• Patients must have evidence of chemotherapy-refractory metastatic CRPC following standard antiandrogen withdrawal (AAWD); CRPC will be defined as patients with metastatic prostate cancer with radiologic evidence of metastases on either bone scan, plain x-rays, CT scans, chest x-ray, and castrate levels of testosterone ( =< 50 mg/dL)
• All patients must be receiving ongoing therapy to ensure testicular androgen suppression (LHRH therapy or bilateral orchiectomy)
• Patients must have received prior Docetaxel-based or Mitoxantrone-based chemotherapy; previous chemotherapy treatments must be completed at least 4 weeks prior to screening, and patients must not have any residual therapy-related toxicity present at screening
• Patients must be off any steroids 7 days prior to the initiation of treatment
• Patients must have evidence of disease progression defined as any of the following:
• a) New sites of metastatic disease on radiographic imaging (bone scan or CT scan of chest/abdomen/pelvis) as determined by the referring physician
• b) PSA progression, defined as 2 consecutive PSA rise at least 2 weeks apart with PSA value over a baseline level of at least 5.0 ng/mL, confirmed after an interval of at least two weeks
• ECOG performance status 0-2 (Eastern Cooperative Oncology Group)
• Absolute neutrophil count >= 1500/uL
• Hemoglobin >= 8 g/dL (blood transfusion not permitted within 2 weeks prior to first dose of treatment)
• Platelets >= 100,000/uL
• Serum creatinine =< 1.5 x ULN
• Total bilirubin =< 1.5 x ULN
• AST (aspartate aminotransferase-SGOT) and ALT (SGPT) that are =< 2.5 x ULN (5 x ULN in patients with liver metastasis)
• Fasting cholesterol =< 350mg/dL and fasting triglycerides =< 400mg/dL
• Hemoglobin A1c (HgbA1c) < 10% (optimal therapy permitted)
• Therapeutic INR/PT for those patients receiving oral anticoagulation
• Urine protein:creatinine ratio (UPC) =< 1.0 at screening
• QTc interval =< 450 msec for males and =< 470 msec for females
• The use of cholesterol medications is allowed during the study
• Patients with a history of a prior malignancy are eligible provided they were treated with curative intent and have been disease-free for the time period considered appropriate by the treating physician
• Sexually active men whose sexual partners are women of childbearing potential must agree to use a medically acceptable form of barrier contraception or abstinence during their participation in the study and for at least six weeks after study drug discontinuation
• Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy within 4 weeks prior to starting therapy or throughout the study
• Prior radiopharmaceuticals (strontium, samarium) must be completed at least 8 weeks prior to treatment initiation in this study and all major side effects resolved to =< grade 1
• Patients receiving any other hormonal therapy, including any dose of Megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), must discontinue the agent for at least 4 weeks prior to enrollment
• Life expectancy of at least 12 weeks
• Written informed consent/HIPAA (Health Insurance Portability and Accountability Act)authorization must be provided prior to the performance of any study-related procedures

Exclusion

• Prior treatment with AVASTIN, temsirolimus, everolimus or sirolimus
• Evidence of current or prior central nervous system (CNS) metastases or any imaging abnormality indicative of CNS metastases; patients with history of cord compression are eligible provided they had either palliative radiation therapy or surgery, have NO neurologic symptoms (as determined by treating physician), have stable spinal disease by scans and are off any steroids prior to initiating study drug (at least 7 days)
• Major surgery or radiation therapy within 28 days prior to screening (Palliative radiotherapy to painful bone lesions is allowed within 14 days prior to study entry); subject must have recovered from prior surgery and radiation
• Significant cardiovascular disease defined as congestive heart failure (NYHA Class II, III, or IV), angina pectoris requiring nitrate therapy, or myocardial infarction within the last 6 months
• Inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy
• History of stroke or transient ischemic attack within 6 months prior to screening
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease
• Known congenital long QT syndrome, history of Torsade de pointes or ventricular tachycardia
• Known pulmonary hypertension or pneumonitis
• More than 1 episode of DVT/PE within the last 6 months
• Evidence or history of bleeding diathesis or coagulopathy
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to screening
• Supplements or complementary medicines/botanicals are not permitted while on protocol therapy, except for any combination of the following: conventional multivitamin supplements; selenium; lycopene; soy supplements; patients should review the label with their doctor prior to enrollment, and discontinue disallowed agents prior to study enrollment; patients taking St. John's Wort need to discontinue its use at least 7 days prior to initiating trial
• Serious intercurrent infections or non-malignant medical illnesses including uncontrolled autoimmune disorders
• Psychiatric illnesses/social situations that would limit compliance with protocol requirements
• Known contraindication to receive temsirolimus or AVASTIN
• Use of any other experimental drug or therapy within 28 days of baseline
• Immunocompromised subjects, including known seropositivity for human immunodeficiency virus (HIV), or current or chronic hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus [anti HCV] with confirmatory testing) (testing is not mandatory to be eligible for the study)
• Anticancer therapies such as biologic therapy and chemotherapy, as well as radiation therapy or cancer surgery
• Other current or recent (within 4 weeks prior to randomization) investigational agent
• Rifampicin
• Immunosuppressive therapies except steroids
• Prophylactic use of white blood growth factors to support neutrophils
• Concomitant treatment with agents that have CYP3A4 induction or inhibition potential should be voided