Prostate Cancer
Conditions
Brief summary
This is a prospective, single-center, two-phase study to assess the efficacy of single pulsed-dose flutamide in creating double strand breaks (DSBs) in prostate cancer within patients receiving central androgen suppression and brachytherapy.
Detailed description
This is a prospective, single-center, two-phase study to assess the efficacy of single pulsed-dose flutamide in creating DSBs (double strand breaks) in prostate cancer within patients receiving central androgen suppression and brachytherapy. The initial phase is a 6-patient single-arm run-in phase to test feasibility and rule out futility of the intervention. All patients within the run-in phase will receive 50mg flutamide prior to brachytherapy and prostatic biopsy. If futility is ruled out (\>1 patients with DSBs on biopsy), then accrual will continue in the randomized, double-blind phase. Subjects will be randomized in a 2:1 ratio (12:6 patients), for an all-trial total of 18 patients receiving flutamide vs 6 patients receiving placebo.
Interventions
DRUGFlutamide
50mg flutamide prior to brachytherapy and prostatic biopsy
OTHERPlacebo
placebo prior to brachytherapy and prostatic biopsy
Sponsors
Patrick C. Walsh Fund
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The initial phase is a 6-patient single-arm run-in phase to test feasibility and rule out futility of the intervention. All patients within the run-in phase will receive 50mg flutamide prior to brachytherapy and prostatic biopsy. If futility is ruled out (\>1 patients with DSBs on biopsy), then accrual will continue in the randomized in a 2:1 ratio (12:6 patients), for an all-trial total of 18 patients receiving flutamide vs 6 patients receiving placebo.
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed prostate cancer * At least one biopsy core with Gleason 7 or higher disease * The patient has decided to undergo brachytherapy plus androgen suppression as treatment modality for his prostate cancer (with or without supplemental external beam radiation) * Suitable volume of disease for biopsy: * clinically palpable disease corresponding to (ipsilateral to) any involved core on biopsy * Signed study-specific consent form prior to registration
Exclusion criteria
* Known hypersensitivity or allergic response to flutamide * Severe hepatic impairment * Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fold-change Post Flutamide Exposure | Post Flutamide exposure up to 12 hours | To confirm DNA double-strand breaks occur in prostate cancer tissue following pulse-dose flutamide administration in patients who are androgen suppressed. A value less than 1 indicates a decrease and a value greater than 1 indicates an increase. |
Countries
United States
Participant flow
Pre-assignment details
All participants in the run-in phase received flutamide. In the second phase, additional participants were randomized, double-blind phase to receive Flutamide or Placebo
Participants by arm
| Arm | Count |
|---|---|
| Run-In 6-patient single-arm run-in phase to test feasibility and rule out futility of the intervention.
Patients within the run-in phase will receive 250mg prior to brachytherapy and prostatic biopsy | 6 |
| Flutamide 250mg flutamide prior to brachytherapy and prostatic biopsy
Flutamide: 250mg flutamide prior to brachytherapy and prostatic biopsy | 14 |
| Placebo placebo prior to brachytherapy and prostatic biopsy
Placebo: placebo prior to brachytherapy and prostatic biopsy | 5 |
| Total | 25 |
Baseline characteristics
| Characteristic | Flutamide | Placebo | Total | Run-In |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 1 Participants | 13 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 12 Participants | 2 Participants |
| Age, Continuous | 65.86 years | 60.20 years | 64.76 years | 66 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United States | 14 Participants | 5 Participants | 25 Participants | 6 Participants |
| Sex/Gender, Customized Male Participants | 14 Participants | 5 Participants | 25 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 14 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 0 / 14 | 1 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 14 | 0 / 5 |
Outcome results
Primary
Fold-change Post Flutamide Exposure
To confirm DNA double-strand breaks occur in prostate cancer tissue following pulse-dose flutamide administration in patients who are androgen suppressed. A value less than 1 indicates a decrease and a value greater than 1 indicates an increase.
Time frame: Post Flutamide exposure up to 12 hours
Population: Patients with tumor tissue at biopsy. Patients that received Flutamide in Phase 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Flutamide | Fold-change Post Flutamide Exposure | 5.860 Fold-change |