Safety and Tolerability Study of ISIS EIF4E Rx in Combination With Docetaxel and Prednisone (CRPC)

Inclusion Criteria

• •Provide written informed consent prior to Screening.
• •Age ≥ 18 years.
• •Histological or cytological diagnosis of adenocarcinoma of the prostate.
• •Metastatic disease for which no curative therapy exists and for which systemic chemotherapy is indicated.
• •Progression of disease despite either medical or surgical castration. If the patient received medical androgen ablation, a castrate level of testosterone (\> or = 50 ng/dL) must have been present concurrent with disease progression. Progressive disease is defined as any one of the following:
• •* Rising serum PSA levels: two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart with the value of the third point being ≥ 2 ng/mL. If the third PSA level is less than the second, an additional fourth test to confirm a rising PSA (i.e., the fourth value is ≥ the second value and is ≥ 2 ng/mL) is acceptable.
• •* Progressive measurable disease defined as an 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.
• •* Bone progressions: appearance of 2 or more new lesions on bone scan or other imaging.
• •If patient did not have a surgical orchiectomy:
• •* The patient must be on androgen suppression treatment (e.g. LHRH agonist), have a castrate level of testosterone (\< or = 50 ng/dL), and must be willing to continue the treatment throughout the study.
• •* The patient must have discontinued treatment with anti-androgens (discontinued ≥ 4 weeks for flutamide and ≥ 6 weeks for nilutamide or bicalutamide prior to Screening) and have documented disease progression following discontinuation.
• •PSA \> or = 2 ng/mL during the Screening period.
• •Performance status of 0 or 1 on the ECOG Performance Status Scale.
• •Have an estimated life expectancy of at least 12 weeks.
• •Adequate organ function within 14 days prior to first study dose (ISIS EIF4E Rx or docetaxel, whichever occurs first) including the following:
• •* Absolute neutrophil count (ANC) \> or = 1.5 x 109/L.
• •* Platelet count \> or = 100 x 109/L.
• •* Total bilirubin \< or = 1.0 x upper limit of normal (ULN).
• •* Aspartate aminotransferase (AST) \< or = 1.5 x ULN.
• •* Alanine aminotransferase (ALT) \< or = 1.5 x ULN.
• •* Serum creatinine \< or = 1.5 x ULN.
• •* Prothrombin time (PT) and international normalized ratio (INR) within normal limits.
• •* Activated partial thromboplastin time (aPTT) within normal limits.
• •Part 1: Have had no more than 1 prior chemotherapy or biological therapy regimen (approved or experimental; all previous hormonal therapies are allowed and not counted as biological therapy for this inclusion criterion) for prostate cancer. This does not include treatments that may have been received in the adjuvant or neoadjuvant setting. A regimen is defined as two or more consecutive cycles of treatment. Part 2: Have had no prior chemotherapy or biological therapy (approved or experimental; all previous hormonal therapies are allowed and not counted as biological therapy for this inclusion criterion) in any setting for prostate cancer.
• •Have discontinued all previous therapies for cancer (except treatment with LHRH analogues) as follows:
• •* Hormone therapies (e.g., abiraterone, MDV3100) must have been discontinued 4 weeks prior to screening.
• •* Radiotherapy must be discontinued at least 4 weeks prior to screening, and the patient must have recovered from the acute effects of therapy.
• •Recovery from all toxicities of prior therapy to ≤ Grade 2 by NCI CTCAE, version 4.0 (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).
• •Men of reproductive potential must agree to use an effective form of contraception, as determined by the Investigator, during the treatment period of the study and for 10 weeks following the last dose of study drug.
• •The patient is willing and able to comply with the study visit schedule and procedures, and geographic proximity (Investigator's discretion) that allows adequate follow-up.