A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study Comparing AT-101 in Combination With Docetaxel and Prednisone Versus Docetaxel and Prednisone in Men With Chemotherapy-Naïve Metastatic Hormone Refractory Prostate Cancer (HRPC)
1. Males age ≥ 18 years with histologically confirmed adenocarcinoma of the prostate,
which is now metastatic (e.g. any T, any N, M1a-c) based on bone scan, CT scan, or
2. Progression of disease despite androgen deprivation (androgen ablation or surgical
castration) and anti-androgen withdrawal as documented by one or more of the
- Progression of measurable disease per RECIST
- Bone scan progression, defined as the appearance of ≥ 2 new lesions on bone
scan, attributable to prostate cancer
- Rising PSA, as defined by increasing levels on at least two consecutive
assessments, following a prior assessment taken as a reference value, where all
of the following are met:
- The assessments are at least one week apart, with the first assessment at
least one week later than the reference value
- Progressive increase in the two assessments after the reference value,
without an intervening decrease between assessments.
- The last value prior to study entry is ≥ 2 ng/mL
3. Serum testosterone level ≤ 50 ng/dL post orchiectomy or while maintained on
continuous or intermittent medical androgen suppression with a LHRH agonist or
4. At least 2 weeks since ketoconazole or systemic steroids (any dose); 2 weeks since
prior flutamide, megestrol, or aminoglutethimide; and at least 2 weeks since prior
bicalutamide or nilutamide
5. Radiation therapy and/or therapy with samarium must have been completed 4 weeks prior
to first dose of therapy. Strontium therapy must have been completed at least 12
weeks prior to the first dose of therapy. The patient must have recovered from all
6. ECOG performance status ≤ 2
7. Able to swallow and retain oral medication
1. Received prior chemotherapy (including estramustine phosphate [Estracyt]) for HRPC.
Adjuvant chemotherapy (including docetaxel) is allowed provided that progression of
disease occurred ≥ 6 months after the completion of adjuvant therapy.
2. Patients must not be receiving concurrent anti-androgen hormonal therapy for HRPC
(LHRH directed therapies are acceptable to maintain castrate levels of testosterone).
3. Treatment with monoclonal antibody (e.g., VEGF targeting antibody) or prostate cancer
vaccine within 45 days prior to the first dose of study treatment. Acute toxicities
from prior therapy must have resolved to Grade ≤ 1.
4. Known history of or clinical evidence of central nervous system (CNS) metastases or
5. Active secondary malignancy or history of other malignancy within the last 5 years
6. Prior history of radiation therapy to ≥ 30% of the bone marrow
7. Peripheral neuropathy of ≥ Grade 2
8. Patients with malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel are excluded.
Subjects with ulcerative colitis, inflammatory bowel disease, or partial or complete
small bowel obstruction are also excluded.
9. Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional
10. Known active symptomatic fungal, bacterial and/or viral infection including active
HIV. Note: screening for viruses is not required.
11. Psychiatric illness/social situations that would limit compliance with the study