To Lengthen the Duration of the Off-Treatment of Intermittent Androgen Suppression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00283803
Recruitment Status : Unknown
Verified February 2008 by University of Washington.
Recruitment status was:  Active, not recruiting
First Posted : January 30, 2006
Last Update Posted : February 21, 2008
OSI Pharmaceuticals
Information provided by:
University of Washington

Brief 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.

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 an 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 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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Flutamide Drug: Leuprolide Acetate Drug: Exisulind Phase 2

Detailed Description:

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 PSA. If not already obtained, you will have a bone scan and a CT scan to establish a baseline.

You will be receiving hormone suppression treatment with monthly injections of an LH-RH 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of the Effect of Exisulind on the Duration of the "Off-Treatment" Interval on Patients With Biochemical Relapse of Prostate Cancer Who Are Treated With Intermittent Androgen Suppression
Study Start Date : October 2001
Estimated Primary Completion Date : December 2010
Estimated Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Drug: Flutamide
250 mg tid
Drug: Leuprolide Acetate
7.5 mg q month
Other Name: Lupron
Drug: Exisulind
Exisulind 125 mg
Other Name: no other names

Primary Outcome Measures :
  1. To determine whether the addition of exisulind to the treatment of patients who have completed at least ONE cycle of IAS will extend the "off-treatment" cycle. [ Time Frame: to be determined ]

Secondary Outcome Measures :
  1. To determine the time to hormone-refractory diseases in the patients who are taking exisulind with IAS [ Time Frame: to be determined ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00283803

United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
OSI Pharmaceuticals
Principal Investigator: Celestia Higano, MD University of Washington

Responsible Party: Celestia Higano, University of Washington Identifier: NCT00283803     History of Changes
Other Study ID Numbers: 01-9710-A04
First Posted: January 30, 2006    Key Record Dates
Last Update Posted: February 21, 2008
Last Verified: February 2008

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Sulindac sulfone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists
Anticarcinogenic Agents
Protective Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic