Trial Outcomes & Findings for Exisulind and Intermittent Androgen Suppression (ADT) in Biochemical Relapsed Prostate Cancer (NCT NCT00283803)

Last Updated: 2018-08-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

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

Results posted on

2018-08-07

Participant Flow

Study enrolled 32 subjects who had developed biochemical progression of prostate cancer, shown by the rising prostate specific antigen level (PSA) after curative therapy (either a radical prostatectomy or external beam irradiation). Trial was open to enrollment 2002 through 2004.

Approximately 40 patients were considered. A total of 32 were accrued between 12Mar2002 and 29Oct2004. Patients not enrolled either failed to meet eligibility criteria or withdrew consent prior to treatment. 19 patients completed study and were evaluable for study endpoints.

Participant milestones

Participant milestones
Measure	Exisulind Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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. Exisulind: Exisulind 125 mg
Overall Study STARTED	32
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Exisulind Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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. Exisulind: Exisulind 125 mg
Overall Study Physician Decision	9
Overall Study Withdrawal by Subject	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IAS and Exisulind n=32 Participants Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants
Age, Categorical >=65 years	17 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	32 Participants n=5 Participants

PRIMARY outcome

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

Population: Of the 32 patients who enrolled, 19 were evaluable.

Outcome measures

Outcome measures
Measure	IAS and Exisulind n=19 Participants Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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.
Duration of the First "Off-treatment" Cycle in Patients Who Have Completed One Cycle of Intermittent Androgen Suppression With the Addition of Exisulind.	39 Weeks Interval 25.0 to 71.0

PRIMARY outcome

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

Population: Out of 32 enrolled patients, 19 met criteria to be evaluable.

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).

Outcome measures

Outcome measures
Measure	IAS and Exisulind n=19 Participants Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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.
Time to Hormone-refractory Diseases in Patients Treated With Intermittent Androgen Suppression and Exisulind	286 Weeks Interval 15.6 to Maximum range of time to CRPC is N/A because some patients did not become Castrate Resistant prior to end of study.

PRIMARY outcome

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

Population: Of 32 enrolled patients, 19 met criteria to be evaluable for study.

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

Outcome measures

Outcome measures
Measure	IAS and Exisulind n=19 Participants Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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.
Number of Participants With Dose Hold, Dose Reduction, or Treatment Withdrawal for Toxicity. Dose Hold for Toxicity	6 Participants
Number of Participants With Dose Hold, Dose Reduction, or Treatment Withdrawal for Toxicity. Dose Reduction for Toxicity	9 Participants
Number of Participants With Dose Hold, Dose Reduction, or Treatment Withdrawal for Toxicity. Treatment Withdrawn for Toxicity	7 Participants

Adverse Events

Exisulind

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Exisulind n=32 participants at risk Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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. Exisulind: Exisulind 125 mg
Gastrointestinal disorders Gallstone with cholecystectomy	3.1% 1/32 • Number of events 1 • 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.
Infections and infestations Pneumonia	3.1% 1/32 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	Exisulind n=32 participants at risk Patients will receive intermittent dosing of hormone therapy with commercially supplied LHRH agonist and antiandrogen 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. Exisulind: Exisulind 125 mg
Investigations Elevated LFTs	31.2% 10/32 • 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.
General disorders Fatigue	25.0% 8/32 • 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.
Renal and urinary disorders Nocturia	21.9% 7/32 • 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.
General disorders Hot Flashes	21.9% 7/32 • 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.
Respiratory, thoracic and mediastinal disorders Shortness of Breath	18.8% 6/32 • 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.
Infections and infestations Congested Sinuses/Cold	18.8% 6/32 • 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.
Investigations Anemia	15.6% 5/32 • 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.
Musculoskeletal and connective tissue disorders Back Pain	15.6% 5/32 • 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.
Investigations Hypertriglyceridemia/Hyperlipidemia	15.6% 5/32 • 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.
Renal and urinary disorders Renal Insufficiency	12.5% 4/32 • 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.
Musculoskeletal and connective tissue disorders Pain/Soreness/Cramps - leg(s)	12.5% 4/32 • 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.
Gastrointestinal disorders Diarrhea	12.5% 4/32 • 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.
Metabolism and nutrition disorders Hyperglycemia	9.4% 3/32 • 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.
Metabolism and nutrition disorders Weight loss	9.4% 3/32 • 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.
Cardiac disorders Hypertension	9.4% 3/32 • 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.
Psychiatric disorders Depression	9.4% 3/32 • 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.
Metabolism and nutrition disorders Weight Gain	9.4% 3/32 • 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.
Reproductive system and breast disorders Decreased Libido	9.4% 3/32 • 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.

Additional Information

Dr. Celestia Higano, MD

University of Washington

Phone: 206-606-1187

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place