Adenocarcinoma of the Prostate, Recurrent Prostate Cancer
Conditions
Keywords
sulforaphane, broccoli sprout extract (BSE), prostate cancer, recurrent prostate cancer, phase II
Brief summary
This phase II trial studies how well sulforaphane works in treating patients with recurrent prostate cancer. Sulforaphane may prevent or slow the growth of certain cancers.
Detailed description
PRIMARY OBJECTIVES: I. To determine the proportion of patients who achieve a 50% decline in prostate-specific antigen (PSA) levels within 20 weeks of sulforaphane treatment. SECONDARY OBJECTIVES: I. To determine the percentage change in PSA from baseline to the final measured value at the end of study as well as the maximal PSA decline that occurs while on study for each subject. II. To determine the proportion of patients whose PSA has not doubled after full 20 weeks of sulforaphane treatment. III. To determine the safety profile of sulforaphane. IV. To determine the pharmacokinetics (PK) of sulforaphane and its metabolites in blood. V. To determine the effect of sulforaphane supplementation on target pharmacodynamic (PD) modulation in peripheral blood cells. VI. To assess the effect of Glutathione-S-Transferase Mu 1 (GSTM1) genotype on sulforaphane PK, PD. VII. To collect frozen serum for future analysis of correlative biomarkers. OUTLINE: Patients receive sulforaphane orally (PO) once daily for 20 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 14-30 days and every 6 months for 12 months.
Interventions
DRUGSulforaphane
Sulforaphane given 200μmol (total daily) orally in four 50μmol capsules taken once daily from Week 1 Day 1 to Week 20 Day 7. On days when clinic visits are required patient must wait to take that day's dose until instructed to do so in clinic.
OTHERLaboratory biomarker analysis
Correlative studies
OTHERPharmacological study
Correlative studies
Sponsors
The Wayne D. Kuni and Joan E. Kuni Foundation
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathologically or cytologically proven adenocarcinoma of the prostate treated with either a prostatectomy or definitive radiation (external beam or brachytherapy * Protocol-Specific Prostate Working Group 2 (PCWG2) Criteria: rising PSA after definitive therapy * For post surgical patients: the nadir reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met and values 3A or #4 are 1.0 ng/mL or higher * For post radiation therapy patients: the nadir reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met and if values 3A or #4 are 2.0 ng/mL or more above the nadir reference value (#1) according to Phoenix/American Society for Therapeutic Radiology and Oncology (ASTRO) criteria * Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 * The following laboratory results within 4 weeks prior to starting study treatment: * White blood cells (WBC) \>= 3000/mm\^3 * Neutrophil \>= 1,500/mm\^3 * Platelet \>= 100,000/mm\^3 * Serum creatinine =\< upper limit of normal (ULN) * Albumin \> 3.0 gm/dL * Total bilirubin \< 1.5 X ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 1.5 X ULN * Testosterone level \>= 150ng/dL, and no evidence of progression while on prior hormonal therapy, if applicable (i.e. patient must be non-castrate resistant). * Prior androgen therapy is allowed as long as the patient did not progress while on therapy. * The following imaging scans within 12 weeks prior to starting study treatment: Whole Body Bone Scan: computed tomography (CT) Chest/Abdomen/Pelvis w/ contrast; NOTE: if contrast medium for CT scan is contraindicated for the patient, documentation of this is required and a CT scan with contrast will not be required; subject still must obtain a CT without contrast, though. * Willingness to use effective contraception by study participants or their female partners throughout the treatment period and for at least 2 months following treatment * Signed informed patient consent and Health Insurance Portability and Accountability Act (HIPAA) within 3 months prior to starting treatment
Exclusion criteria
* Significant active medical illness which in the opinion of the investigator would preclude protocol treatment * Measurable and/or evaluable recurrent prostate cancer by imaging (CT scan of the chest, abdomen, and pelvis and bone scan performed within 12 weeks prior to starting treatment) or by physical exam * Prior investigational therapy within 30 days prior to starting study treatment * Prior treatment with a known histone deacetylase inhibitor (including but not limited to valproic acid, suberoylanilide hydroxamic acid \[SAHA\],Panobinostat (LBH589), etc) within 6 months prior to starting study treatment or while on study therapy * Concurrent systemic treatment for prostate cancer * Current treatment with warfarin * Gastrointestinal ailments which would interfere with the ability to adequately absorb sulforaphane * Allergy to cruciferous vegetables * Any condition which, in the opinion of the study clinician, would make participation in the study harmful to the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Achieve a 50% Decline in Prostate-Specific Antigen (PSA) Levels | Less than or equal to 20 weeks of sulforaphane treatment. | To determine the proportion of patients who achieve a decline in PSA levels while receiving sulforaphane treatment. as a measure of anti-tumor activity in men with recurrent prostate cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Percent Change in PSA (i.e., the Smallest Increase for Those With Increased PSA and the Greatest Decline for Those With Decreased PSA) | PSA measured every 28 days while on study treatment, an average of 5 months | — |
| Proportion of Patients Whose PSA Levels Have Not Doubled | While on treatment with sulforaphane (less than or equal to 20 weeks.) | — |
| Incidence of Grade 3 or Higher Treatment Related Toxicity | Continually through study and 14-30 days after last drug dose. | Toxicities will be graded based on the NIH Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria of Adverse Events Version 4.0 (http://ctep.cancer.gov). All adverse events of any grade (for example, abnormal laboratory values, etc.) deemed clinically significant by the investigator will be recorded as a measure of the safety profile of sulforaphane |
| Percent Change in PSA From Baseline to Final Measured Value at End of Study | Measure at baseline and after stopping study treatment (less than or equal to 20 weeks of treatment with sulforaphane.) | To determine the percentage change in PSA from baseline to the final measured value at the end of study. |
| Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype | Day 1 of study treatment | — |
| Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype | Day 1 of study treatment | — |
| Half-life of Sulforaphane (SFN) in Blood | Day 1 of study treatment | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulforaphane Sulforaphane given 200μmol (total daily) orally in four 50μmol capsules taken once daily from Week 1 Day 1 to Week 20 Day 7. On days when clinic visits are required patient must wait to take that day's dose until instructed to do so in clinic. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Sulforaphane |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 70.6 years STANDARD_DEVIATION 6.8 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Proportion of Patients Who Achieve a 50% Decline in Prostate-Specific Antigen (PSA) Levels
To determine the proportion of patients who achieve a decline in PSA levels while receiving sulforaphane treatment. as a measure of anti-tumor activity in men with recurrent prostate cancer.
Time frame: Less than or equal to 20 weeks of sulforaphane treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulforaphane | Proportion of Patients Who Achieve a 50% Decline in Prostate-Specific Antigen (PSA) Levels | 5 percentage of participants |
Secondary
Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype
Time frame: Day 1 of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sulforaphane | Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype | 2.1 hours |
Secondary
Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype
Time frame: Day 1 of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sulforaphane | Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype | 2.6 Hours |
Secondary
Half-life of Sulforaphane (SFN) in Blood
Time frame: Day 1 of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sulforaphane | Half-life of Sulforaphane (SFN) in Blood | 2.2 hours |
Secondary
Incidence of Grade 3 or Higher Treatment Related Toxicity
Toxicities will be graded based on the NIH Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria of Adverse Events Version 4.0 (http://ctep.cancer.gov). All adverse events of any grade (for example, abnormal laboratory values, etc.) deemed clinically significant by the investigator will be recorded as a measure of the safety profile of sulforaphane
Time frame: Continually through study and 14-30 days after last drug dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulforaphane | Incidence of Grade 3 or Higher Treatment Related Toxicity | 0 participants |
Secondary
Minimum Percent Change in PSA (i.e., the Smallest Increase for Those With Increased PSA and the Greatest Decline for Those With Decreased PSA)
Time frame: PSA measured every 28 days while on study treatment, an average of 5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sulforaphane | Minimum Percent Change in PSA (i.e., the Smallest Increase for Those With Increased PSA and the Greatest Decline for Those With Decreased PSA) | 2 percent change |
Secondary
Percent Change in PSA From Baseline to Final Measured Value at End of Study
To determine the percentage change in PSA from baseline to the final measured value at the end of study.
Time frame: Measure at baseline and after stopping study treatment (less than or equal to 20 weeks of treatment with sulforaphane.)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sulforaphane | Percent Change in PSA From Baseline to Final Measured Value at End of Study | 35 Percent change |
Secondary
Proportion of Patients Whose PSA Levels Have Not Doubled
Time frame: While on treatment with sulforaphane (less than or equal to 20 weeks.)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sulforaphane | Proportion of Patients Whose PSA Levels Have Not Doubled | 90 percentage of participants |