Trial Outcomes & Findings for Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer (NCT NCT01787331)

Last Updated: 2020-02-05

Results Overview

The number of patients with biochemically relapsed disease after prior definitive local therapy who achieve a ≥ 50% decline from baseline in serum PSA after 12 weeks of therapy with itraconazole, confirmed by repeat measurement at least 2 weeks later.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

At 12 weeks after start of treatment

Results posted on

2020-02-05

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Itraconazole) Patients receive twice/day 300mg itraconazole (oral)
Overall Study STARTED	21
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Itraconazole) Patients receive twice/day 300mg itraconazole (oral)
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Itraconazole) n=21 Participants Patients receive twice/day 300mg itraconazole (oral)
Age, Customized 40-49 Years	1 participants n=5 Participants
Age, Customized 50-59 Years	1 participants n=5 Participants
Age, Customized 60-69 Years	10 participants n=5 Participants
Age, Customized 70-79 Years	9 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	0 Participants n=5 Participants
Race (NIH/OMB) White	20 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
Years since diagnosis of prostate cancer	7.83 years n=5 Participants
Gleason Grade at Time of Diagnosis Gleason grade ≤ 7 (low/intermediate grade)	14 Participants n=5 Participants
Gleason Grade at Time of Diagnosis Gleason grade > 7 (high grade)	7 Participants n=5 Participants
Time interval from biochemical relapse to study entry	4.01 years n=5 Participants
PSA doubling time at the time of study entry	5.72 months n=5 Participants

PRIMARY outcome

Timeframe: At 12 weeks after start of treatment

Outcome measures

Outcome measures
Measure	Treatment (Itraconazole) n=19 Participants Patients receive twice/day 300mg itraconazole (oral)
Number of Patients Who Achieve a Greater Than or Equal to 50% Decline in Serum Prostate Specific Antigen (PSA)	1 Participants

SECONDARY outcome

Timeframe: Up to 12 weeks

The mean percent change in PSA doubling time from pre-treatment to after 12 weeks of protocol therapy

Outcome measures

Outcome measures
Measure	Treatment (Itraconazole) n=19 Participants Patients receive twice/day 300mg itraconazole (oral)
Mean Percent Change in PSA Doubling Time	-0.64 Percent change in PSA doubling time Interval -59.96 to 71.38

SECONDARY outcome

Timeframe: Up to 2 years

PSA progression defined as: 1. If no PSA decline is observed on therapy, PSA progression will be defined as an increase in serum PSA \> 50% above the baseline PSA, and an absolute increase of \> 2 ng/mL above baseline, confirmed by repeat measurement at least 2 weeks later. 2. If PSA declines on therapy, PSA progression will be defined as an increase in serum PSA \> 50% above the nadir PSA on therapy, and an absolute increase \> 2 ng/mL above the nadir, confirmed by repeat measurement at least 2 weeks later. The probability distribution of the time to PSA progression will be estimated using the Kaplan-Meier product limit method measured from the start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Treatment (Itraconazole) n=19 Participants Patients receive twice/day 300mg itraconazole (oral)
Median Time to PSA Progression	4.68 months Interval 2.0 to 21.7

SECONDARY outcome

Timeframe: Up to 2 years

Population: Only 1 patient displayed clinical progression

Clinical progression will be defined as the first occurrence of either the development of metastases or initiation of non-protocol therapy, and will exclude PSA-only progression. The probability distribution of the time to clinical progression will be estimated using the Kaplan-Meier product limit method measured from the time of start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Treatment (Itraconazole) n=1 Participants Patients receive twice/day 300mg itraconazole (oral)
Median Time to Clinical Progression	21.7 months Interval 21.7 to 21.7

SECONDARY outcome

Timeframe: Up to 2 years

Population: Data not collected

The probability distribution of the time to first metastasis will be estimated using the Kaplan-Meier product limit method measured from the time of start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome measures
Measure	Treatment (Itraconazole) n=21 Participants Patients receive twice/day 300mg itraconazole (oral)
Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs Blood Pressure	14.3 percentage of participants
Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs Weight	0 percentage of participants
Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs Pulse	0 percentage of participants
Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs Respiration Rate	0 percentage of participants
Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs Temperature	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 years

All patients who receive at least one dose of study drug will be analyzed for safety endpoints. All adverse events will be graded and classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4.. Percentage of patients with grade 1 or higher, treatment-related adverse events based on the following labs will be reported: potassium, sodium, alkaline phosphatase, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Hematocrit, Hemoglobin, platelets, white blood cells, atypical lymphs, basophils, eosinophils, monocytes, neutrophils, blood urea nitrogen, and creatinine.

Outcome measures

Outcome measures
Measure	Treatment (Itraconazole) n=21 Participants Patients receive twice/day 300mg itraconazole (oral)
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Potassium	9.52 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Alanine aminotransferase	4.76 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Sodium	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Alkaline phosphatase	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Total bilirubin	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Aspartate aminotransferase	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Hematocrit	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Hemoglobin	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Platelets	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events White blood cells	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Atypical lymphs	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Basophils	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Eosinophils	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Monocytes	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Neutrophils	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Blood urea nitrogen	0 percentage of participants
Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events Creatinine	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: No data collected

Descriptive statistics including the mean, standard deviation, and range of steady-state trough serum levels of itraconazole and its active metabolite hydroxy-itraconazole will be determined.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 4 weeks

Population: No data collected

Descriptive statistics including the mean, standard deviation, and range of steady-state trough serum levels of itraconazole and its active metabolite hydroxy-itraconazole will be determined.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Itraconazole)

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Itraconazole) n=21 participants at risk Patients receive twice/day 300mg itraconazole (oral)
Cardiac disorders Atrial flutter	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Infections and infestations Lung infection	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Infections and infestations Sepsis	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Investigations - Other, specify	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Renal and urinary disorders Renal and urinary disorders - Other, specify	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Pulmonary edema	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events

Other adverse events

Other adverse events
Measure	Treatment (Itraconazole) n=21 participants at risk Patients receive twice/day 300mg itraconazole (oral)
General disorders Edema limbs	57.1% 12/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
General disorders Fatigue	42.9% 9/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
General disorders Gait disturbance	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
General disorders General disorders and administration site conditions - Other, specify	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
General disorders Non-cardiac chest pain	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Constipation	14.3% 3/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Diarrhea	14.3% 3/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Nausea	14.3% 3/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Abdominal pain	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Dry mouth	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Gastroesophageal reflux disease	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Abdominal distension	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Bloating	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Flatulence	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Alanine aminotransferase increased	23.8% 5/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Aspartate aminotransferase increased	19.0% 4/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Blood bilirubin increased	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Lymphocyte count decreased	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Neutrophil count decreased	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations Weight loss	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Investigations White blood cell decreased	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Dyspnea	19.0% 4/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Cough	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Hoarseness	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Sinus disorder	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Sore throat	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Respiratory, thoracic and mediastinal disorders Wheezing	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Vascular disorders Hypertension	28.6% 6/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Vascular disorders Hot flashes	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Vascular disorders Lymphedema	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Metabolism and nutrition disorders Hypokalemia	28.6% 6/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Metabolism and nutrition disorders Anorexia	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Metabolism and nutrition disorders Hyperglycemia	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Infections and infestations Upper respiratory infection	23.8% 5/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Infections and infestations Rhinitis infective	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Infections and infestations Urinary tract infection	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Nervous system disorders Dizziness	19.0% 4/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Nervous system disorders Headache	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Nervous system disorders Cognitive disturbance	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Nervous system disorders Dysgeusia	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Nervous system disorders Paresthesia	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Skin and subcutaneous tissue disorders Dry skin	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Skin and subcutaneous tissue disorders Rash maculo-papular	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Skin and subcutaneous tissue disorders Nail ridging	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Skin and subcutaneous tissue disorders Photosensitivity	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Musculoskeletal and connective tissue disorders Pain in extremity	9.5% 2/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Cardiac disorders Atrial flutter	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Cardiac disorders Chest pain - cardiac	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Cardiac disorders Heart failure	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Cardiac disorders Sinus bradycardia	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Psychiatric disorders Depression	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Psychiatric disorders Libido decreased	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Renal and urinary disorders Urinary frequency	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Renal and urinary disorders Urinary incontinence	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Endocrine disorders Adrenal insufficiency	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events
Reproductive system and breast disorders Erectile dysfunction	4.8% 1/21 • Up to 2 years All patients who received at least one dose of study drug were analyzed for adverse events

Additional Information

Rahul Aggarwal, MD

University of California, San Francisco

Phone: 877-827-3222

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place