R-(-)-Gossypol and Androgen Ablation Therapy in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms; Adenocarcinoma
Intervention: AT-101; Bicalutamide; LHRH agent
Intervention description: AT101 will be administered orally 20 mg/day for 21 days of a 28 day cycle.; Daily bicalutamide 50 mg po is encouraged for the first month of LHRH agonist therapy to prevent a flare. Continued bicalutamide use is optional. Bicalutamide will be administered orally at a dose of 50 mg po daily, Day 1 to 28 of each cycle.; An LHRH agonist(Leuprolide Acetate or Goserelin)can be administered at standard dosing appropriate to the agent used.
Intervention MeSH terms: Acetic Acid; Bicalutamide; Gossypol acetic acid; Gossypol; Hormones
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate Cancer; adenocarcinoma of the prostate; stage IV prostate cancer; newly diagnosed stage IV prostate cancer

Summary:

      This phase II trial is studying how well giving gossypol together with androgen ablation
      therapy works in treating patients with newly diagnosed metastatic prostate cancer. Gossypol
      may stop the growth of tumor cells by blocking blood flow to the tumor. Androgens can cause
      the growth of prostate tumor cells. Luteinizing hormone-releasing hormone agonists and drugs,
      such as bicalutamide, may lessen the amount of androgens made by the body. Giving gossypol
      together with androgen ablation therapy may be an effective treatment for prostate cancer
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologically proven adenocarcinoma of the prostate with clinical stage D2 disease
             defined by soft tissue or bony metastasis.

          -  Patients must have elevated PSA ≥ 5 ng/ml within 12 weeks prior to registration.
             Androgen ablation therapy, which must include an LHRH agonist, will begin 6 weeks
             prior to initiation of AT101.

          -  Patients are allowed prior local therapy with radiation or surgery. Patients must not
             have received more than 12 months of androgen ablation therapy or antiandrogen therapy
             in the adjuvant/neoadjuvant setting and no prior androgen ablation therapy for
             metastatic disease, beyond the six week induction period prior to initiation of AT101.
             Patients with prior adjuvant/neoadjuvant androgen ablation therapy must have completed
             such therapy at least 12 months prior.

          -  Must be 18 years old or older.

          -  Life expectancy of greater than 6 months.

          -  ECOG performance status ≤ 2.

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocytes ≥ 3,000/mcL

               -  absolute neutrophil count ≥ 1,500/mcL

               -  platelets ≥ 100,000/mcL

               -  total bilirubin within normal institutional limits

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels
                  above institutional normal

          -  There must be no plans to receive concomitant chemotherapy or radiation therapy during
             the study period. Baseline and on study PSA values must be obtained from the same
             reference laboratory.

          -  The effects of AT101 on the developing human fetus at the recommended therapeutic dose
             are unknown. For this reason men and/or their partners must agree to use adequate
             contraception, (including hormonal or barrier method of birth control, abstinence)
             prior to study entry and for the duration of study participation.

        Exclusion Criteria

          -  Patients who have had radiotherapy within 4 weeks prior to entering the study or those
             who have not recovered from adverse events due to agents administered more than 4
             weeks earlier.

          -  Patients may not be receiving any other investigational agents.

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AT101 or other agents used in the study.

          -  Patients with bilateral orchiectomy are not eligible.

          -  Patients presenting with acute cord compression are not eligible.

          -  History of bowel obstruction or GI dismotility disorder.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Any condition (e.g., gastrointestinal tract disease resulting in an inability to take
             oral medication or a requirement for IV alimentation, prior surgical procedures
             affecting absorption, or active peptic ulcer disease) that impairs their ability to
             swallow and retain AT-101 tablets.

          -  Requirement for routine use of hematopoietic growth factors (including granulocyte
             colony stimulating factor, granulocyte macrophage colony stimulating factor, or
             interleukin-11) or platelet transfusions to maintain absolute neutrophil counts or
             platelets counts above the required thresholds for study entry.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with AT-101.