Prostate Cancer
Conditions
Brief summary
The purpose of this study is to determine if the drug dutasteride increases expression of genes that slow the growth of prostate cancer during treatment with intermittent androgen ablation therapy (hormone therapy).
Detailed description
We have shown in a murine model of treatment with intermittent androgen ablation therapy of prostate cancer that when dutasteride is given during the regrowth phase (off-phase) of intermittent therapy, that tumor growth is inhibited and that survival is improved. We have also shown that testosterone is a more potent inducer of certain tumor suppressor androgen response genes than dihydrotestosterone. In this murine model, we showed that use of a 5-alpha reductase inhibitor (dutasteride) resulted in significant hyperinduction of the U19 tumor suppressor androgen response gene during the regrowth phase of treatment. In the current clinical trial, we will determine if use of dutasteride in men with advanced prostate cancer during the off-phase of intermittent androgen ablation therapy will also result in hyperinduction of these tumor suppressor androgen response genes. Gene expression will be measured in tumor tissue obtained by prostate biopsies during the off-phase when the testosterone level has normalized. Prostate-specific antigen (PSA) levels will also be measured to determine the PSA doubling time during the off-phase to determine the effect of dutasteride on PSA kinetics.
Interventions
DRUGDutasteride
0.5 mg capsule given orally on daily basis
DRUGPlacebo
Identical placebo
Sponsors
University of Chicago
Northwestern University
Endeavor Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven prostate cancer * Patients are hormone-naive * Patients either to begin androgen ablation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or already receiving therapy with LHRH agonist * Advanced prostate cancer with either positive pelvic nodes or bone/visceral metastasis * Must have an intact prostate (no previous surgery or XRT) * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Recovery from any major infection or surgical procedure * Signed informed consent
Exclusion criteria
* Known intolerance or allergy to dutasteride * Concomitant chemotherapy, biologic therapy, or XRT to prostate * Bilateral orchiectomy * Prior malignancy within 5 years of registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Expression of U19 Gene in Tumor From Prostate Gland During First Off-cycle. | At the end of off-cycle 1 defined by when the testosterone level reaches normal (approximately 6 months) | Calculation of the level of gene expression of the U19 tumor suppressor gene compared between the 2 arms at the end of off-treatment cycle 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of Prostate-specific Antigen (PSA) Doubling Time During First Off-cycle | At month 9 and ongoing monthly until end of off-cycle 1 defined by when the testosterone level reaches normal (approximately 6 months) | Calculation of number of months when baseline PSA doubles compared between the 2 arms at the end of off-treatment cycle 1. |
Countries
United States
Participant flow
Pre-assignment details
20 participants enrolled and all received initial treatment with anti-androgen therapy (AAT) for planned 8 months (on-cycle 1). 7 participants progressed during this treatment, so 13 participants proceeded with randomization.
Participants by arm
| Arm | Count |
|---|---|
| A: Dutasteride During First Off-Cycle Arm A patients received dutasteride (0.5 mg/day) during the first off-cycle and received placebo during the second off-cycle
Dutasteride: 0.5 mg capsule given orally on daily basis | 10 |
| B: Placebo During First Off-Cycle Arm B patients received placebo during the first off-cycle and received dutasteride (0.5 mg/day) during the second off-cycle
Placebo: Identical placebo | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Off-cycle | Cancer progression | 1 | 0 |
| Second AAT Treatment (On-cycle 2) | Cancer progression | 2 | 1 |
Baseline characteristics
| Characteristic | B: Placebo During First Off-Cycle | Total | A: Dutasteride During First Off-Cycle |
|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 20 | 67 years STANDARD_DEVIATION 20 | 67 years STANDARD_DEVIATION 20 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 20 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 0 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Relative Expression of U19 Gene in Tumor From Prostate Gland During First Off-cycle.
Calculation of the level of gene expression of the U19 tumor suppressor gene compared between the 2 arms at the end of off-treatment cycle 1.
Time frame: At the end of off-cycle 1 defined by when the testosterone level reaches normal (approximately 6 months)
Population: Only patients from each arm with biopsies at the end of off-cycle 1 are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Dutasteride During First Off-Cycle | Relative Expression of U19 Gene in Tumor From Prostate Gland During First Off-cycle. | 0.24 Relative expression | Standard Deviation 0.5 |
| B: Placebo During First Off-Cycle | Relative Expression of U19 Gene in Tumor From Prostate Gland During First Off-cycle. | 0.28 Relative expression | Standard Deviation 0.45 |
Secondary
Determination of Prostate-specific Antigen (PSA) Doubling Time During First Off-cycle
Calculation of number of months when baseline PSA doubles compared between the 2 arms at the end of off-treatment cycle 1.
Time frame: At month 9 and ongoing monthly until end of off-cycle 1 defined by when the testosterone level reaches normal (approximately 6 months)
Population: Only patients from each arm with biopsies at the end of off-cycle 1 are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Dutasteride During First Off-Cycle | Determination of Prostate-specific Antigen (PSA) Doubling Time During First Off-cycle | 1.42 Months | Standard Deviation 0.8 |
| B: Placebo During First Off-Cycle | Determination of Prostate-specific Antigen (PSA) Doubling Time During First Off-cycle | 1.56 Months | Standard Deviation 0.9 |