Clinical trial NCT01228084: Sulforaphane in Treating Patients With Recurrent Prostate Cancer
Official title: The Effects of Sulforaphane in Patients With Biochemical Recurrence of Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Keywords: sulforaphane
broccoli sprout extract (BSE)
prostate cancer
recurrent prostate cancer
phase II
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: The Wayne D. Kuni and Joan E. Kuni Foundation
First posted: 2010-10-25
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Patients Who Achieve a 50% Decline in Prostate-Specific Antigen (PSA) Levels
timeFrame: Less than or equal to 20 weeks of sulforaphane treatment.
Secondary outcomes:
measure: Percent Change in PSA From Baseline to Final Measured Value at End of Study
timeFrame: Measure at baseline and after stopping study treatment (less than or equal to 20 weeks of treatment with sulforaphane.)
measure: Minimum Percent Change in PSA (i.e., the Smallest Increase for Those With Increased PSA and the Greatest Decline for Those With Decreased PSA)
timeFrame: PSA measured every 28 days while on study treatment, an average of 5 months
measure: Proportion of Patients Whose PSA Levels Have Not Doubled
timeFrame: While on treatment with sulforaphane (less than or equal to 20 weeks.)
measure: Incidence of Grade 3 or Higher Treatment Related Toxicity
timeFrame: Continually through study and 14-30 days after last drug dose.
measure: Half-life of Sulforaphane (SFN) in Blood
timeFrame: Day 1 of study treatment
measure: Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype
timeFrame: Day 1 of study treatment
measure: Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype
timeFrame: Day 1 of study treatment
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Joshi J Alumkal, MD
role: PRINCIPAL_INVESTIGATOR
References: