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.

A study doctor will meet with you and ask you about your medical history, examine you, and explain the study. We will draw some blood for tests (about 4-6 tablespoons), including Prostate-Specific Antigen (PSA). If not already obtained, you will have a bone scan and a computed tomography scan (CT scan) to establish a baseline.

You will be receiving hormone suppression treatment with monthly injections of a luteinizing hormone-releasing hormone (LHRH) analog such as Lupron or Zoladex and an antiandrogen such as Eulexin or Casodex as part of your standard care for prostate cancer. About 3 months before your next "off-treatment" period, you will start 1 Exisulind pill 250 mg (2 x 125mg capsules) by mouth twice a day. It is necessary for you to start the Exisulind treatment 3 months prior to your next "off-treatment" period so that the medication can build up in your system enough to be effective.

Per our standard follow-up procedures, we will ask you to have blood draws every 2 weeks for up to 12 weeks after starting Exisulind to check liver function. Thereafter you will be asked to have monthly blood draws, and return to the clinic every 3 months for a physical examination, to determine how well you are tolerating the study medication, how your cancer is responding to the treatment, and to give you more study medication. You will continue taking Exisulind during your "off-treatment" period until your PSA reaches a threshold level. PSA threshold is defined by your primary treatment. If you have had your prostate removed, the threshold is 1.0 ng/dL. If you have an intact prostate, your threshold is 4 ng/dL. Once your PSA reaches this level, you will restart your hormone suppression treatment as directed by your doctor.

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

Adverse Events collected for each patient from time of starting Exisulind through time of study withdraw, assessed up to 10 years.

The term "adverse event" could include any of the following events that arise or increase in severity and/or frequency during the course of the study:

• signs or symptoms
• clinically significant laboratory abnormality
• abnormality detected during physical exam

These data will be recorded regardless of whether they are thought to be associated with the study or the drug under investigation.

Enrollment goal was 35 evaluable patients. Of the 40+ considered, 32 consented and enrolled. However 13 withdrew, leaving only 19 evaluable patients. Due to small sample size, results were primarily descriptive in nature.