Clinical trial NCT01083368 (phase 1/phase 2, status: completed)
Conditions: prostate cancer
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: temsirolimus
SMILES: CN1N=NC2=C(N=CN2C1=O)C(N)=O
Eligibility criteria:

        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