OGX-427 in Castration Resistant Prostate Cancer Patients

Inclusion Criteria

* Age ≥ 18 years on the date of consent.
* ECOG performance status of 0 or 1.
* Histological or cytological diagnosis of adenocarcinoma of the prostate.
* Metastatic disease on chest, abdominal, or pelvic CT and/or bone scan for which no curative therapy exists.
* Progression of prostate cancer. Progression is defined by one or more of the following:

  1. Increasing serum PSA level: two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. The last confirmation PSA value must be obtained within the 14 days prior to randomization. A minimum starting value of 2.0 ng/mL is required for study randomization.
  2. Progressive measurable disease: at least a 20% increase in the sum of the diameters of measurable lesions over the smallest sum observed or the appearance of one or more new lesions as assessed by CT scan. Measurable lesions are nodal or visceral soft-tissue lesions with nodal lesions ≥ 15 mm in diameter at the shortest axis and visceral/soft-tissue lesions ≥ 10 mm in longest diameter (See Section 6.4).
  3. Bone Progression: appearance of 2 or more new lesions on bone scan (or other imaging).
* All patients who have not had a surgical orchiectomy must continue treatment with LHRH agonist or antagonist to maintain a castrate level of testosterone.
* Patient must fulfill "Prior Therapy" criteria as follows:

  1. Chemotherapy: No prior chemotherapy for metastatic disease is permissible. (Exception: neoadjuvant/adjuvant chemotherapy if received \> 12 months prior to randomization.)
  2. Hormone therapy: prior surgical or medical castration therapy is required. Prior treatment with non-steroidal antiandrogens, abiraterone or other experimental hormone therapy (e.g. MDV3100, YAK-700) is allowed provided a minimum of at least 14 days have passed since completing therapy and randomization in the study.
  3. Experimental therapy: prior non-cytotoxic experimental therapy is permitted provided a minimum of at least 14 days has passed since completing therapy prior to randomization.
  4. Radiation: prior external beam radiation is permitted provided a minimum of at least 28 days have passed since completing radiotherapy at the time of randomization (or following disease progression and prior to receiving therapy at the time of cross-over). Exception for radiotherapy: at least 7 days must have passed since completing single fraction of ≤ 800 cGy.
  5. Corticosteroids: prior corticosteroid therapy is permitted. Within 4 days following randomization, all patients must be taking prednisone 5 mg BID.
* Baseline laboratory values as stated below:

  1. ANC ≥ 1.5 x 109 cells /L, platelet count ≥ .100 x 109 /L, and hemoglobin ≥ 9 g/dL without transfusion.
  2. Creatinine ≤ 1.5 x upper limit of normal (ULN).
  3. Total bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's disease).
  4. SGPT (ALT) and SGOT (AST) ≤ 2.5 x ULN.
  5. Castrate serum testosterone level (\< 50 ng/dL-or-\< 1.7 nmol/L).
* Recovery from all toxicities of prior therapy to ≤ grade 2 by NCI CTCAE, version 3.0. (Exception: any toxicity that in the view of the Investigator is not a clinically significant safety risk for further therapy administration, including, but not limited to: anemia, fatigue, erectile dysfunction, hot flashes, lymphedema of an extremity, dizziness, cough, and urinary incontinence).
* Must be willing to use effective contraception, if of child bearing potential, throughout study treatment and for 3 months after completion of study treatment.
* Must be willing not to change (add or subtract) bone protecting therapy (bisphosphonates and/or denosumab) during the study unless changed for toxicity.
* Written informed consent must be obtained prior to any protocol-specific procedures being performed.

Exclusion Criteria

* Unable to tolerate a dose of 10 mg of prednisone a day.
* Requiring an amount of opioids to control pain \> 30 mg of a morphine-equivalent per day.
* Known coagulopathy or actively receiving warfarin (Coumadin) therapy.
* Documented brain metastases, or carcinomatous meningitis, treated or untreated (Brain imaging for asymptomatic patients is not required).
* Current symptomatic cord compression requiring surgery or radiation therapy (once successfully treated and there has been no progression, patients are eligible for the study).
* Active second malignancy (except adequately treated non-melanomatous skin cancer or other solid tumors curatively treated with no evidence of disease \> 3 years).
* History of allergic reactions to therapeutic antisense oligonucleotides.
* Uncontrolled medical conditions such as heart failure, myocardial infarction, uncontrolled hypertension, stroke or treatment of a major active infection within 3 months of randomization, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.
* Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.