Sulforaphane in Treating Patients With Recurrent Prostate Cancer

Adenocarcinoma of the Prostate Clinical Trial

Official title:

The Effects of Sulforaphane in Patients With Biochemical Recurrence of Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01228084
• Other study ID #: 6613
• Secondary ID: SOL-10082-L6613
• Status: Completed
• Phase: Phase 2
• First received: October 19, 2010
• Last updated: April 26, 2017
• Start date: November 2010
• Est. completion date: May 2013

Study information

• Verified date: April 2017
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2013
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostatic Neoplasms
• Recurrent Prostate Cancer

Intervention

Drug:
• 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.

Other:
• Laboratory biomarker analysis
Correlative studies
• Pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	The Wayne D. Kuni and Joan E. Kuni Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Less than or equal to 20 weeks of sulforaphane treatment.
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.	Measure at baseline and after stopping study treatment (less than or equal to 20 weeks of treatment with sulforaphane.)
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)		PSA measured every 28 days while on study treatment, an average of 5 months
Secondary	Proportion of Patients Whose PSA Levels Have Not Doubled		While on treatment with sulforaphane (less than or equal to 20 weeks.)
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	Continually through study and 14-30 days after last drug dose.
Secondary	Half-life of Sulforaphane (SFN) in Blood		Day 1 of study treatment
Secondary	Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype		Day 1 of study treatment
Secondary	Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype		Day 1 of study treatment