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

NCT00283803 | Completed Phase 2 Results

• 2 other identifiers: 44830EX1006
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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 (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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Duration of the First "Off-treatment" Cycle in Patients Who Have Completed One Cycle of Intermittent Androgen Suppression With the Addition of Exisulind.

  Patients were monitored for the amount of time (number of weeks) that passed between the completion of a cycle of Intermittent Androgen Suppression with Exisulind and the need to re-initiate treatment with Intermittent Androgen Suppression. It was hoped that adding Exisulind to standard Androgen Suppression would extend the amount time before disease progression.

  From date of first treatment until the date of first documented progression or study withdrawal, whichever came first, assessed up to 10 years.

• Time to Hormone-refractory Diseases in Patients Treated With Intermittent Androgen Suppression and Exisulind

  Patients were monitored for continued hormonal sensitivity of their disease from the time of the first treatment with Intermittent Androgen Suppression and Exisulind and the time at which point they were considered hormone-refractory (castrate resistant). The development of hormone-refractory disease was one of the criteria for withdraw from study treatment. For this protocol, hormone-refractory was defined as 2 consecutive rising PSAs at least 2 weeks apart while on an LHRH agonist (with or without an anti-androgen).

  From date of first treatment until the date of first documented progression or study withdrawal, whichever came first, assessed up to 10 years.

• Number of Participants With Dose Hold, Dose Reduction, or Treatment Withdrawal for Toxicity.

  Patients were monitored for toxicity related treatment modifications from the start of Exisulind through the time that there were withdrawn from study.

  From date of first treatment until study withdrawal, assessed up to 10 years.

Study Arms (1)

IAS and Exisulind

EXPERIMENTAL

Patients will receive intermittent dosing of hormone therapy with commercially supplied luteinizing hormone-releasing hormone (LHRH) agonist and anti-androgen to be chosen by physician per standard of care. Exisulind will be started 3 months prior to the end of the second cycle of hormone therapy. Patients will continue treatment with Exisulind beyond the completion of the second cycle of hormone therapy until they meet criteria for discontinuation.

Drug: Exisulind; Drug: luteinizing hormone-releasing hormone (LHRH) agonist; Drug: Antiandrogen

Interventions

Exisulind DRUG

Oral antineoplastic agent that induces apoptosis in cancerous cells.

Also known as: Aptosyn

IAS and Exisulind

luteinizing hormone-releasing hormone (LHRH) agonist DRUG

Hormonal therapy to suppress testosterone as a standard treatment for Prostate Cancer.

Also known as: Lupron, Zoladex

IAS and Exisulind

Antiandrogen DRUG

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.

Also known as: Eulexin, Casodex

IAS and Exisulind

Eligibility Criteria

• Age: 21 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A willingness and ability to sign an informed consent document;
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• OSI Pharmaceuticals: collaborator

Study Sites (1)

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

sulindac sulfone; Gonadotropin-Releasing Hormone; Leuprolide; Goserelin; Androgen Antagonists; Flutamide; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Celestia Higano, MD
• Organization: University of Washington

mjcampbe@seattlecca.org

206-606-1187

Study Officials

• Celestia Higano, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine, Division of Oncology & Urology

Study Record Dates

• First Submitted: January 26, 2006
• First Posted: January 30, 2006
• Study Start: March 12, 2002
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: August 7, 2018
• Results First Posted: May 14, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)