Exisulind and Intermittent Androgen Suppression (ADT) in Biochemical Relapsed Prostate Cancer

• Status: Completed
• Trial end date: 2011-10-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborator: OSI Pharmaceuticals
• Treatments: Androgen Antagonists; Androgens; Flutamide; Hormones; Leuprolide; Prolactin Release-Inhibiting Factors; Sulindac; Sulindac sulfone

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