Prostate Cancer
Conditions
Brief summary
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
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
Interventions
DRUGNoni extract
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.
Sponsors
University of Hawaii Cancer Research Center
University of Hawaii
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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 2. Very low risk and low risk groups will be confirmed by Oncotype DX prostate cancer test and provided a Genomic Prostate Score (GPS) 3. 55 years of age and older (\>/= 55 years) at the time of informed consent 4. No evidence of extraprostatic disease on 3T multiparametric pelvic MRI 5. No baseline PT/PTT abnormalities, coagulopathies, or who are on any blood thinners. 6. ECOG performance status 0-2 7. 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 8. Willing to comply with proposed visit and treatment schedule 9. Able to understand and willing to sign a written informed consent document
Exclusion criteria
1. Prior history of treated prostate cancer 2. Concomitant use of medications that are known CYP3A4 substrates 3. 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 4. 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) 5. Use of any blood thinners. 6. Consumption or use of any Noni or Noni-containing products 7. 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 8. Participation in any other investigational study or use of any other investigational agents within 30 days prior to study entry 9. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare Genomic Prostate Score (GPS) in Prostatic Tumors | Change from screening and at 12 months or early termination | 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. |
| Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Change from screening and at 12 months or early termination | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | Baseline and 9 months | 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. |
| Frequency of Adverse Events | Enrollment, 1, 3, 6, 9, and 12 months, and 7 days post treatment | Tolerability of Noni extract in men diagnosed with very low risk or low risk prostate cancer as assessed by CTCAE v4.0 |
| 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. | Enrollment and 12 months or at early termination | 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. |
| 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. | Enrollment and 12 months or at early termination | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Noni 6,000 mg/Day Noni extract 6,000 mg/day (4 capsules with breakfast, 4 capsules with lunch and 4 capsules with dinner)
Noni extract: 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. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Noni 6,000 mg/Day |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 2 / 6 |
Outcome results
Primary
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.
Time frame: Change from screening and at 12 months or early termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Noni 6,000 mg/Day | Compare Genomic Prostate Score (GPS) in Prostatic Tumors | GPS Pt 1 Baseline | 37 scores on a scale |
| Noni 6,000 mg/Day | Compare Genomic Prostate Score (GPS) in Prostatic Tumors | GPS Pt 2 Baseline | 34 scores on a scale |
| Noni 6,000 mg/Day | Compare Genomic Prostate Score (GPS) in Prostatic Tumors | GPS Pt 3 Baseline | 17 scores on a scale |
| Noni 6,000 mg/Day | Compare Genomic Prostate Score (GPS) in Prostatic Tumors | GPS Pt 4 Baseline | 36 scores on a scale |
| Noni 6,000 mg/Day | Compare Genomic Prostate Score (GPS) in Prostatic Tumors | GPS Pt 5 Baseline | 38 scores on a scale |
| Noni 6,000 mg/Day | Compare Genomic Prostate Score (GPS) in Prostatic Tumors | GPS Pt 6 Baseline | 39 scores on a scale |
Primary
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.
Time frame: Change from screening and at 12 months or early termination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores pre therapy Pt 1 | 1 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Core post therapy Pt 1 | 6 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores pre therapy Pt 2 | 2 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores post therapy Pt 2 | 5 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores pre therapy Pt 3 | 1 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores post therapy Pt 3 | 3 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores pre therapy Pt 4 | 1 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores post therapy Pt 4 | 0 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores pre therapy Pt 5 | 1 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores post therapy Pt 5 | 0 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores pre therapy Pt 6 | 1 positive cores |
| Noni 6,000 mg/Day | Number of Positive Cores Associated With Participants Disease Progression of Prostate Cancer | Positive Cores post therapy Pt 6 | 0 positive cores |
Secondary
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.
Time frame: Baseline and 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA Baseline Pt 1 | 4.4 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA Baseline Pt 2 | 5.4 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA Baseline Pt 3 | 7.3 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA Baseline Pt 4 | 9.7 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA Baseline Pt 5 | 6.9 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA Baseline Pt 6 | 7.9 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA 9 Month Pt 1 | 5.7 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA 9 Month Pt 2 | 9.6 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA 9 Month Pt 3 | 10.2 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA 9 Month Pt 4 | 6.9 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA 9 Month Pt 5 | 8.1 ng/mL |
| Noni 6,000 mg/Day | Effects of Noni Extract on Serum Prostate Specific Antigen (PSA) Levels | PSA 9 Month Pt 6 | 7.7 ng/mL |
Secondary
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.
Time frame: Enrollment and 12 months or at early termination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Noni 6,000 mg/Day | 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. | MVD Pre Treatment | 60.5 microvessel/mm^2 | Standard Deviation 18.1 |
| Noni 6,000 mg/Day | 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. | MVD Post Treatment | 41.2 microvessel/mm^2 | Standard Deviation 9.5 |
Secondary
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.
Time frame: Enrollment and 12 months or at early termination
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Noni 6,000 mg/Day | 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. | Apoptosis Pre Treatment | 12.2 percentage of positive cells | Standard Deviation 3.2 |
| Noni 6,000 mg/Day | 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. | Proliferation Pre Treatment | 1.2 percentage of positive cells | Standard Deviation 0.3 |
| Noni 6,000 mg/Day | 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. | Apoptosis Post Treatment | 10.9 percentage of positive cells | Standard Deviation 2.1 |
| Noni 6,000 mg/Day | 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. | Proliferation Post Treatment | 1.4 percentage of positive cells | Standard Deviation 0.4 |
Secondary
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
Time frame: Enrollment, 1, 3, 6, 9, and 12 months, and 7 days post treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Noni 6,000 mg/Day | Frequency of Adverse Events | 3 Adverse Events Reported |