Exisulind and Intermittent Androgen Suppression (ADT) in Biochemical Relapsed Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Exisulind; luteinizing hormone-releasing hormone (LHRH) agonist; Antiandrogen
Intervention description: Oral antineoplastic agent that induces apoptosis in cancerous cells.; Hormonal therapy to suppress testosterone as a standard treatment for Prostate Cancer.; Hormonal therapy used as lead in treatment with luteinizing hormone-releasing hormone (LHRH) agonist to prevent the initial rise in testosterone (testosterone flare) seen during the first dose of LHRH agonists.
Intervention MeSH terms: Sulindac sulfone; Hormones; Prolactin Release-Inhibiting Factors; Androgen Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Male
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to determine if an investigational drug called
      Exisulind will extend the "off-treatment" period of patients receiving Intermittent Androgen
      Suppression (ADT).

      There is evidence suggesting that alternating between periods of treatment and no treatment
      with androgen suppressants may delay the time to develop androgen-insensitive progression and
      improve overall quality of life. During intermittent androgen suppression (IAS) treatments,
      men receive a luteinizing hormone-releasing hormone (LHRH) agonist and antiandrogen for a
      fixed period of time (approximately 9 months) and then enter an off-treatment period, whose
      length will vary, depending on the rate of rise in the patient's Prostate-Specific Antigen
      (PSA). Once the PSA reaches an established threshold (1 ng/mL in men who have had a
      prostatectomy or 4 ng/ml in men with an intact prostate), androgen suppression will be
      re-initiated for another 9 months. These cycles of on-treatment/off-treatment will be
      repeated until patient no longer responds to the androgen suppression and it is clear that
      their cancer is progressing. It has been observed that off-treatment periods tend to become
      shorter with each successive cycle of androgen suppression, presumably due to the emergence
      of androgen-independent clones. This study proposes to look at exisulind, a pro-apoptotic
      drug, which may extend the off-treatment period in patients receiving IAS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A willingness and ability to sign an informed consent document;

               -  21 years or of legal age;

          -  Histologically or cytologically documented prostate cancer.

          -  ECOG Performance status score of 0 or 1.

          -  Received at least one cycle of IAS with an LHRH agonist and anti-androgen

          -  Willingness to remain off chronic NSAIDs (with the exception of ibuprofen or
             naproxen), including COX 2 inhibitors and salicylates (e.g., aspirin, mesalamine,
             azodisalicylate, salsalate, sulfasalazine) for duration of the study. Patients on low
             dose aspirin for cardiovascular prevention may be included in the study.

          -  Have not taken sulindac (Clinoril™) on regular basis for any indication for one week
             prior to enrollment and willing to remain off of sulindac for the duration of the
             study.

          -  Patients with prior radiation must be 2 weeks from their last radiation-treatment and
             have recovered from all associated toxicity.

        Exclusion Criteria:

          -  Known hypersensitivity to sulindac (Clinoril™)

          -  ECOG Performance status score > 1;

          -  Patients previously on SWOG 9346 or 9921 trials, or any other trials using IAS for
             which adding exisulind may be confounding.

          -  Patients may not have any evidence of hormone-refractory prostate cancer, i.e. 2
             consecutive rises in PSA on LHRH agonist and anti-androgen

          -  Active peptic ulcer disease;

          -  Use of an investigational medication or device within one month of initiating study
             therapy;

          -  Elevations of serum creatinine to above the upper limit of normal;

          -  Platelet count < 100,000/L; hgb < 9.0 g/dL; absolute neutrophil count < 1500/mm3

          -  Known hepatic, biliary tract, renal or hematologic dysfunction which in the opinion of
             the Investigator or Sponsor are clinically significant or would obscure laboratory
             analyses or are associated with lab abnormalities;

          -  Any condition or any medication that may interfere with the conduct of the study.

          -  Bilirubin > ULN. Patients with elevated indirect bilirubin due to Gilbert's Syndrome
             will be eligible.

          -  AST or ALT >2.5 X ULN