Prostate CancerPhase 2NCT00283803
Exisulind and Intermittent Androgen Suppression (ADT) in Biochemical Relapsed Prostate Cancer
A Phase 2 study testing Exisulind, luteinizing hormone-releasing hormone (LHRH) agonist and Antiandrogen in people with Prostate Cancer, run by University of Washington at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Exisulind, luteinizing hormone-releasing hormone (LHRH) agonist and Antiandrogen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2002to Oct 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Seattle Cancer Care Alliance
Seattle, Washington, 98109
About this study
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 (ADT)
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.
Read the 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 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.
- Conditions
- Prostate Cancer
- Being tested
- Exisulind, luteinizing hormone-releasing hormone (LHRH) agonist, Antiandrogen
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExisulindDrug
Also called Aptosyn
Oral antineoplastic agent that induces apoptosis in cancerous cells.
luteinizing hormone-releasing hormone (LHRH) agonistDrug
Also called Lupron, Zoladex
Hormonal therapy to suppress testosterone as a standard treatment for Prostate Cancer.
AntiandrogenDrug
Also called Eulexin, Casodex
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Exisulind; Drug: luteinizing hormone-releasing hormone (LHRH) agonist; Drug: Antiandrogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: From date of first treatment until study withdrawal, assessed up to 10 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2006 (estimated)
- Study start12 Mar 2002
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- OSI Pharmaceuticals
- Responsible party
- Principal investigator, Celestia Higano, University of Washington
- Investigators
- Celestia Higano, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00283803
- Sponsor's protocol ID
- 44830
- Other IDs
- EX1006
- Status last verified
- Aug 2018
- First submitted
- 26 Jan 2006
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 (ADT)
- ClinicalTrials.gov ID
- NCT00283803
- Acronym / sponsor ID
- 44830
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- OSI Pharmaceuticals
- Study start
- 12 Mar 2002 (actual)
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 30 Jan 2006 (estimated)
- Results
- Posted 14 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IAS and Exisulind | Experimental | Drug: Exisulind, Drug: luteinizing hormone-releasing hormone (LHRH) agonist, Drug: AntiandrogenPatients 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- A willingness and ability to sign an informed consent document;
- 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.
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ExisulindAlso: AptosynOral antineoplastic agent that induces apoptosis in cancerous cells. | Drug | IAS and Exisulind |
| luteinizing hormone-releasing hormone (LHRH) agonistAlso: Lupron, ZoladexHormonal therapy to suppress testosterone as a standard treatment for Prostate Cancer. | Drug | IAS and Exisulind |
| AntiandrogenAlso: Eulexin, CasodexHormonal 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. | Drug | IAS and Exisulind |
Primary outcome
Duration of the First "Off-treatment" Cycle in Patients Who Have Completed One Cycle of Intermittent Androgen Suppression With the Addition of Exisulind.
Time frame: From date of first treatment until the date of first documented progression or study withdrawal, whichever came first, assessed up to 10 years.
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.
Time to Hormone-refractory Diseases in Patients Treated With Intermittent Androgen Suppression and Exisulind
Time frame: From date of first treatment until the date of first documented progression or study withdrawal, whichever came first, assessed up to 10 years.
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).
Number of Participants With Dose Hold, Dose Reduction, or Treatment Withdrawal for Toxicity.
Time frame: From date of first treatment until study withdrawal, assessed up to 10 years.
Patients were monitored for toxicity related treatment modifications from the start of Exisulind through the time that there were withdrawn from study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Celestia Higano, MD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Exisulind, luteinizing hormone-releasing hormone (LHRH) agonist and Antiandrogen in people with Prostate Cancer, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of the First "Off-treatment" Cycle in Patients Who Have Completed One Cycle of Intermittent Androgen Suppression With the Addition of Exisulind. (time frame: From date of first treatment until the date of first documented progression or study withdrawal, whichever came first, assessed up to 10 years.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2018.