Sulforaphane in Treating Patients With Recurrent Prostate Cancer

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01228084
• Collaborator: The Wayne D. Kuni and Joan E. Kuni Foundation (Other)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 30
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Recurrent Prostate Cancer	Drug: Sulforaphane; Other: Laboratory biomarker analysis; Other: Pharmacological study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. To determine the proportion of patients whose PSA has not doubled after full 20 weeks of sulforaphane treatment.

3. To determine the safety profile of sulforaphane. IV. To determine the pharmacokinetics (PK) of sulforaphane and its metabolites in blood.

4. To determine the effect of sulforaphane supplementation on target pharmacodynamic (PD) modulation in peripheral blood cells.

5. To assess the effect of Glutathione-S-Transferase Mu 1 (GSTM1) genotype on sulforaphane PK, PD.

6. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effects of Sulforaphane in Patients With Biochemical Recurrence of Prostate Cancer
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

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 Names: Broccoli Sprout Extract (BSE) ; Other: Laboratory biomarker analysis; Correlative studies; Other: Pharmacological study; Correlative studies; Other Names: Pharmacological studies

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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]

3. Proportion of Patients Whose PSA Levels Have Not Doubled [While on treatment with sulforaphane (less than or equal to 20 weeks.)]

4. 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

5. Half-life of Sulforaphane (SFN) in Blood [Day 1 of study treatment]

6. Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype [Day 1 of study treatment]

7. Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype [Day 1 of study treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• The Wayne D. Kuni and Joan E. Kuni Foundation

Investigators

• Principal Investigator: Joshi J Alumkal, MD, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joshi Alumkal, Principal Investigator, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT01228084
• Other Study ID Numbers: 6613; SOL-10082-L; 6613
• First Posted: Oct 25, 2010
• Last Update Posted: Apr 28, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Joshi Alumkal, Principal Investigator, OHSU Knight Cancer Institute: sulforaphane; broccoli sprout extract (BSE); prostate cancer; recurrent prostate cancer; phase II
• Additional relevant MeSH terms: Prostatic Neoplasms; Recurrence; Sulforaphane

Study Results

Participant Flow

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Period Title: Overall Study
STARTED	20
COMPLETED	16
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 20%
>=65 years	16 80%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.6 (6.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	20 100%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Achieve a 50% Decline in Prostate-Specific Antigen (PSA) Levels
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	20
Number [percentage of participants]	5 25%

2. Secondary Outcome

Title	Percent Change in PSA From Baseline to Final Measured Value at End of Study
Description	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.)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	20
Median (Full Range) [Percent change]	35

3. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	20
Median (Full Range) [percent change]	2

4. Secondary Outcome

Title	Proportion of Patients Whose PSA Levels Have Not Doubled
Time Frame	While on treatment with sulforaphane (less than or equal to 20 weeks.)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	20
Number [percentage of participants]	90 450%

5. Secondary Outcome

Title	Incidence of Grade 3 or Higher Treatment Related Toxicity
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	20
Number [participants]	0 0%

6. Secondary Outcome

Title	Half-life of Sulforaphane (SFN) in Blood
Time Frame	Day 1 of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	20
Median (Full Range) [hours]	2.2

7. Secondary Outcome

Title	Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype
Time Frame	Day 1 of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	8
Median (Full Range) [Hours]	2.6

8. Secondary Outcome

Title	Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype
Time Frame	Day 1 of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sulforaphane
Arm/Group Description	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.
Measure Participants	12
Median (Full Range) [hours]	2.1

Adverse Events

Arm/Group Title	Sulpforaphane
Arm/Group Description	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
All Cause Mortality
	Sulpforaphane
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sulpforaphane
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	Sulpforaphane
	Affected / at Risk (%)	# Events
Total	15/20 (75%)
Gastrointestinal disorders
Bloating	4/20 (20%)
Diarrhea	4/20 (20%)
Dyspepsia	4/20 (20%)
Flatulence	7/20 (35%)
Gatrointestinal pain	3/20 (15%)
Nausea	7/20 (35%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.