Clinical Study of Noni Extract in Men With Very Low Risk or Low Risk Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of Noni extract in men diagnosed with very low risk or low risk prostate cancer

Detailed Description
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Efficacy and safety of Noni extract will be assessed in an estimated sample size of 30 subjects. Efficacy will be measured by the induction of favorable gene expression changes on Oncotype Dx Prostate Cancer Test after 12 months of intervention with Noni extract (6,000 mg/day). Other efficacy endpoints include the incidence of tumor progression after 12 months of intervention with Noni extract and serum PSA doubling time. Safety measurements will include the incidence and severity of adverse events, effects on angiogenesis (CD34), cell proliferation (Ki-67), and apoptosis (TUNEL) in prostate tissue biopsy samples from Month 12

Official Title
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Phase II Clinical Study of Noni Extract in Men With Very Low Risk or Low Risk Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Noni extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men with a diagnosis of very low risk (<5% risk of disease relapse after primary treatment, criteria; cT1c, Gleason <6, PSA < 10 ng/mL, fewer than 3 positive biopsy cores < 50% cancer in any core, PSA density < 0.15 ng/mL/g); low risk (10% risk of disease relapse after primary treatment, criteria; cT1-2a, Gleason <6, PSA < 10 ng/mL) prostate cancer Very low risk and low risk groups will be confirmed by Oncotype DX prostate cancer test and provided a Genomic Prostate Score (GPS) 55 years of age and older (>/= 55 years) at the time of informed consent No evidence of extraprostatic disease on 3T multiparametric pelvic MRI No baseline PT/PTT abnormalities, coagulopathies, or who are on any blood thinners. ECOG performance status 0-2 Participants must have normal organ and marrow function as demonstrated by the following parameters being: complete blood count (CBC) - no clinically significant findings complete metabolic profile (CMP) - no clinically significant findings Willing to comply with proposed visit and treatment schedule Able to understand and willing to sign a written informed consent document Exclusion Criteria: Prior history of treated prostate cancer Concomitant use of medications that are known CYP3A4 substrates Use of medications or supplements that are known to affect PSA within 30 days prior to informed consent, including toremifene citrate, finasteride, testosterone, dehydroepiandrosterone (DHEA) or other testosterone-like supplements. No dutasteride within 90 days prior to informed consent Consumption of any concomitant nutritional, herbal supplements, and antioxidants should be taken under the discretion of the investigator. The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment: St. John's wort or hyperforin (potent CYP3A4 enzyme inducer) Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor) Use of any blood thinners. Consumption or use of any Noni or Noni-containing products History of renal or hepatic disease, including history of hepatitis B or C. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any psychological, familial, sociological or other concomitant condition that would not allow adequate compliance with the study protocol Participation in any other investigational study or use of any other investigational agents within 30 days prior to study entry History of allergic reactions attributed to Noni or other compounds of similar chemical or biologic composition to Noni, or the inactive components present in Noni capsules.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noni 6,000 mg/day<br>Noni extract 6,000 mg/day (4 capsules with breakfast, 4 capsules with lunch and 4 capsules with dinner) | Drug: Noni extract<br>* Intervention will be administered on an outpatient basis.Six bottles containing 60 capsules will be dispensed to all participants upon enrollment. Then 12 bottles (at 30-day visit) and 18 bottles (at 3, 6 and 9 month visits) will be dispensed to all participants.<br>* Other names: Healing Noni;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare Genomic Prostate Score (GPS) in Prostatic Tumors | Exploring gene expression changes on Oncotype DX Genomic Prostate Score (GPS). The Oncotype DX assay is a clinically validated 17-gene genomic assay that provides a genomic prostate score (GPS; scale 0-100) measuring the heterogeneous nature of prostate tumors. A higher score means a higher risk of disease. Unfortunately, Genomic Health was unable to run the assay on 12-month prostate biopsy samples in which active cancer was not identified therefore we only have baseline data. | Change from screening and at 12 months or early termination | 
| Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Measure tumor size at screening and compare after 12 months of study participation. Disease progression will be identified by either an increase in Gleason score, increase in positive cores, and/or an increase in tumor volume. | Change from screening and at 12 months or early termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | Comparing the serum Prostate Specific Antigen (PSA) test levels for the duration of the trial in men diagnosed with very low risk or low risk prostate cancer. Measure the duration of time it takes for a subjects Prostate specific antigen level to double. | Baseline and 9 months | 
| Frequency of Adverse Events | Tolerability of Noni extract in men diagnosed with very low risk or low risk prostate cancer as assessed by CTCAE v4.0 | Enrollment, 1, 3, 6, 9, and 12 months, and 7 days post treatment | 
| Explore the Molecular Pathways Contributing to the Activities Associated With Noni Extract in the Prostate Cancer (e.g. Cell Proliferation, and Apoptosis in Prostate Tissue Biopsy Samples) Via Immunohistochemistry (IHC) Staining. | Utilizing prostate tissue biopsy samples and serum blood plasma from participants prior to receiving noni extract and after the subject completes 12 months of receiving noni extract. Apoptosis was quantified based on caspase-3 immunostaining. Proliferation was quantified based on Ki-67 immunostaining. | Enrollment and 12 months or at early termination | 
| Explore the Molecular Pathways Contributing to the Activities Associated With Noni Extract in the Prostate Cancer (e.g., Angiogenesis) in Prostate Tissue Biopsy Samples) Via Immunohistochemistry (IHC) Staining. | Utilizing prostate tissue biopsy samples and serum blood plasma from participants prior to receiving noni extract and after the subject completes 12 months of receiving noni extract. MVD, a surrogate for angiogenesis, was quantified based on CD-31 immunostaining. | Enrollment and 12 months or at early termination |