Clinical trial NCT02648919
Conditions: Prostate Cancer
Sponsor: University of Hawaii
Start date: 2015-12-01; Completion date: 2018-12-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Arms: arm 1: Noni extract 6,000 mg/day (4 capsules with breakfast, 4 capsules with lunch and 4 capsules with dinner)
Interventions: intervention 1: Noni extract
Intervention descriptions: intervention 1: 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.

Protocol documents:
Prot_SAP_000.pdf: 
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CONFIDENTIAL 
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PROTOCOL TITLE:   
 
 
 
Phase II Clinical Study of Noni Extract in Men with Very 
Low Risk or Low Risk Prostate Cancer  
 
PROTOCOL NUMBER:   
 
 
Huang 2015-1 
 
IND Number:  
 
 
 
 
IND 128296 
 
NCT Number:  
NCT02648919 
 
PROTOCOL VERSION DATE: 
 
February 7, 2017 
 
PROTOCOL SPONSOR:  
 
 
University of Hawaii Cancer Center 
 
FUNDING SPONSOR:  
 
 
 
University of Hawaii Cancer Center 
 
PRINCIPAL INVESTIGATOR: 
 
Charles J. Rosser, M.D., M.B.A., F.A.C.S. 
 
SUB-INVESTIGATORS: 
 
            Jeffrey Huang, Pharm.D. 
 
PROTOCOL RESEARCH  
LOCATIONS: 
 
University of Hawaii Cancer Center  
 
 
The Queen’s Medical Center 
701 Ilalo St., 
 
 
 
 
 
1301 Punchbowl Street 
Honolulu, HI 96813 
 
 
 
 
 
Honolulu, HI 96813 
 
Island Urology Oahu, LLC 
 
 
 
 
 
Island Urology Hilo, LLC 
1329 Lusitana Street, Suite 602  
 
 
 
670 Ponahawai St, Ste. 217 
Honolulu, HI 96813 
                        Hilo, HI 96720 
 
 
 
 
 


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List of abbreviations: 
 
CBC 𝒄 diff 
Complete blood count with differential 
CMP  
Complete metabolic profile 
PSA  
Prostate specific antigen 
MRI  
Magnetic resonance imaging 
ECOG  
Eastern cooperative oncology group 
DHEA  
Dehydroepiandrosterone 
GPS  
Genomic Prostate Score 
LUTS  
Lower urinary tract symptoms 
QoL  
Quality of life 
EGF  
Epidermal growth factor 
LFT  
Liver function test 
AE  
Adverse event 
SAE  
Serious adverse event 
HPLC-EC 
High pressure liquid chromatography/electrochemical detection 
UHCC 
University of Hawaii Cancer Center 
HDPE  
High Density Polyethylene 
H&E  
Hematoxylin and eosin 
DSMC  
Data and Safety Monitoring Committee 
CTCAE  
Common Terminology Criteria for AEs  
eCRF  
Electronic case report forms 
PT/PTT 
 
Prothrombin time / Partial Prothrombin Time 
 
 
 
 
 
 


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Phase II Clinical Study of Noni Extract in Men with Very Low Risk or Low Risk Prostate 
Cancer 
Eligibility: 
 
 
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 
confirmed by Oncotype DX prostate cancer test 
 
No prior treatment of prostate cancer with 
surgical, radiation, hormonal therapies 
 
55 years of age and older (≥ 55 years) at the 
time of informed consent 
 
No evidence of extraprostatic disease on pelvic 
MRI 
 
ECOG performance status 0−2 
 
No medications, supplements which can 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 of first noni dose.  
 
No baseline PT/PTT abnormalities, 
coagulopathies or anticoagulant drug use, such 
as heparin, or warfarin (Coumadin) 
 
Consumption of any concomitant nutritional, 
herbal supplements, and antioxidants should be 
taken under the discretion of the investigator.  
 
No current use of Noni or noni-containing 
products 
Initial Laboratory/Radiologic Results must be within 
normal range for age: 
 
 
Complete blood count (CBC 𝑐 diff)  
 
Complete metabolic profile including liver 
function tests (CMP + LFT) 
 
PT/PTT 
 
MRI of the pelvis with contrast 
 
Very low or low risk classification confirmed 
by Oncotype DX Prostate Test. 
 
SCHEMA 
Screening/Pre-Enrollment:  
↓ 
Baseline/Enrollment:  
↓ 
Intervention:  
Self-administration of Noni capsules 
6,000 mg/day in divided doses x 12 months 
with 
Clinic Visits at Months 1, 3, 6, 9 
↓ 
End of Intervention: (Month 12) 
 ↓ 
Post-intervention Follow-up: (7+- 3 days post-treatment) 


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Sample size:  
 
The estimated sample size is a total of 30 subjects with paired biopsies (initial diagnosis and 12 
months) 
 
Endpoints: 
Efficacy (Primary): 
 Induction of favorable gene expression changes on Oncotype Dx Prostate Cancer Test 
after 12 months of intervention with Noni extract (6,000 mg daily)  
 Incidence of tumor progression after 12 months of intervention with Noni extract  
 Serum PSA doubling time 
 
Safety: 
 Primary:  Incidence and severity of AEs 
 Secondary:  Effects on angiogenesis (CD34), cell proliferation (Ki-67) and apoptosis 
(TUNEL) in prostate tissue biopsy samples from month 12 
 
 


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Table of Contents 
OBJECTIVES 
9 
PRIMARY 
9 
SECONDARY 
9 
BACKGROUND 
9 
DISEASE BACKGROUND 
9 
STUDY DRUG 
10 
NONI EXTRACT 
10 
CLINICAL EXPERIENCE: NONI EXTRACTS AND CANCER 
11 
PATIENT ENROLLMENT CRITERIA 
11 
INCLUSION CRITERIA 
11 
EXCLUSION CRITERIA 
12 
INCLUSION OF WOMEN AND MINORITIES 
13 
RECRUITMENT PLAN 
13 
TREATMENT PLAN 
13 
DOSE REGIMEN AND DOSE GROUPS 
13 
CONTRAINDICATIONS 
14 
CONCOMITANT MEDICATIONS 
14 
DOSE MODIFICATIONS 
14 
RULES FOR DOSE SUSPENSION AND DISCONTINUATION 
16 
REPLACEMENT 
17 
ADHERENCE/COMPLIANCE 
17 
PHARMACEUTICAL INFORMATION 
17 
NONI 
17 
RATIONALE FOR DOSE SELECTION AND ADMINISTRATION 
18 
AVAILABILITY 
18 
DRUG ACCOUNTABILITY 
18 
PACKAGING AND LABELS 
19 
STORAGE 
19 
AGENT DESTRUCTION/DISPOSAL 
19 
REGISTRATION/ENROLLMENT/STUDY DURATION 
19 
CLINICAL EVALUATIONS AND PROCEDURES 
21 
SCHEDULE OF EVENTS 
21 
SCREENING VISIT EVALUATION 
22 
ENROLLMENT 
22 
EVALUATIONS DURING STUDY INTERVENTION 
23 
MONTHS 1, 3, 6, 9 
23 
EVALUATIONS AT COMPLETION OF STUDY INTERVENTION (12 MONTHS) 
23 
POST-INTERVENTION FOLLOW-UP PERIOD 
24 
METHODS FOR CLINICAL PROCEDURES 
24 


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PROSTATE BIOPSY 
24 
BLOOD DRAW 
24 
ANTHROPOMETRIC MEASUREMENTS 
24 
COLLECTION OF AE AND CONCOMITANT MEDICATIONS INFORMATION 
25 
DEMOGRAPHICS 
25 
LUTS SCORE ASSESSMENT (AUA BPH SYMPTOM SCORE QUESTIONNAIRE) 
25 
QUALITY OF LIFE ASSESSMENT 
25 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION 
25 
OFF DRUG CRITERIA 
27 
OFF STUDY CRITERIA 
27 
STUDY TERMINATION 
27 
SPECIMEN MANAGEMENT 
28 
LABORATORIES 
28 
COLLECTION AND HANDLING PROCEDURES 
28 
TISSUE SAMPLES 
28 
PROSTATE CANCER PATHOLOGY 
28 
BLOOD SAMPLES 
28 
BLOOD COLLECTION SCHEDULE AND PURPOSE 
29 
PSA (SCREENING, MONTHS 3, 6, 9 AND 12) 
29 
COMPREHENSIVE METABOLIC PANEL (CMP) (SCREENING, MONTHS 3, 6, 9 AND 12) 
29 
CBC (SCREENING AND MONTH 3, 6, 9 AND 12) 
29 
PT/PTT (SCREENING, MONTHS 1, 3, 6, 9, AND 12) 
29 
PLASMA FOR SCOPOLETIN LEVEL ANALYSIS (ENROLLMENT, MONTHS 3, 6 9, AND 12) 
29 
SERUM BANKING FOR FUTURE MECHANISTIC STUDIES (ENROLLMENT, MONTHS 6 AND 12) 
30 
SHIPPING INSTRUCTIONS 
30 
SAMPLE BANKING 
30 
SAMPLE TRACKING 
30 
PLASMA SCOPOLETIN ANALYSIS 
30 
DATA AND SAFETY MONITORING 
31 
REPORTING ADVERSE EVENTS (AES) 
31 
DEFINITION 
31 
REPORTABLE AES 
31 
SEVERITY OF AES 
32 
ASSESSMENT OF RELATIONSHIP OF AE TO TREATMENT 
32 
FOLLOW-UP OF AES 
33 
SERIOUS ADVERSE EVENTS (SAES) 
33 
DEFINITION 
33 
FOLLOW-UP OF SAE 
34 
STUDY MONITORING, AUDITING, AND INSPECTION 
34 
DATA MANAGEMENT 
34 
CASE REPORT FORMS 
34 
SOURCE DOCUMENTS 
34 
RECORD RETENTION 
35 


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STATISTICAL CONSIDERATIONS 
35 
SAMPLE SIZE 
35 
STUDY DESIGN/ENDPOINTS 
35 
ETHICAL AND REGULATORY CONSIDERATIONS 
36 
INFORMED CONSENT 
36 
CONFIDENTIALITY 
36 
PUBLICATION PLAN 
37 
RESOURCE SHARING PLAN 
37 
FUNDING SOURCE 
37 
REFERENCES 
38 
 
Appendix A ....................................................................................................................... ECOG performance status 
Appendix B  ........................................................................ List of Foods, Medications, and Supplements to Avoid 
Appendix C.  .............................................................................................................. Initial Assessment Form 
Appendix D  ...................................................................................................................................... LUTS Evaluation 
Appendix E  ........................................................................................................................................... Quality of Life 
Appendix F  ......................................................................................................................................... Medication Log 
 
 
 


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OBJECTIVES 
 
Primary 
To evaluate the Genomic Prostate Score (GPS, and associated gene expression changes) in 
prostatic tumors in men treated with Noni extract (6,000 mg/day) for one year following 
the diagnosis of very low risk or low risk prostate cancer. 
 
To assess the rate of disease progression of prostate cancer at one year in men treated with 
Noni extract following the diagnosis of very low risk or low risk prostate cancer. 
 
Secondary 
Evaluate effects of Noni extract on serum PSA (i.e., serum PSA doubling time) in men 
diagnosed with very low risk or low risk prostate cancer.  
 
Evaluate the tolerability of Noni extract in men diagnosed with very low risk or low risk 
prostate cancer.  
 
Explore the fundamental molecular pathways contributing to the activities associated with 
Noni extract in the prostate cancer (e.g., angiogenesis (CD34), cell proliferation (Ki-67) 
and apoptosis (TUNEL) in prostate tissue biopsy samples).  
 
Evaluate the effect of Noni extract on lower urinary tract symptoms (LUTS) and quality of 
life (QoL) in men diagnosed with very low risk or low risk prostate cancer.  
 
Create a specimen repository (serum and prostate biopsies) to assess other genetic or 
environmental factors that may influence incidence and progression of prostate cancer, and 
to test future hypotheses related to prostate cancer.   
 
BACKGROUND 
  
Disease Background  
Prostate cancer is the most common malignancy affecting men with an estimated 232,090 
cases per year in the United States [Siegal, 2015].  Despite the high incidence, disease 
related mortality statistics are quite favorable compared to other cancers. Less than one 
third of men diagnosed with prostate cancer will die of disease making it considerably less 
lethal than lung and colorectal cancer which rank first and second in terms of cancer related 
deaths [Siegal, 2015]. The high proportion of PSA-detected cancers in current clinical 
practice is largely responsible for this phenomenon since patients with early prostate cancer 
are now diagnosed at a lower tumor stage and grade compared to in previous years. While 
this may allow for earlier curative therapy of potentially life threatening disease, it also 
identifies a large group of patients with a relatively low risk of disease relapse in whom 
radical therapy may be unnecessary and harmful due to its associated morbidity and costs. 


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The optimal treatment strategy for these patients with early prostate cancer (i.e., very low 
risk and low risk disease) is the focus of this proposal and will be addressed in the following 
paragraphs. 
 
Identification of the ideal patient population is fundamental to the development of 
appropriate treatment strategy. For patients with prostate cancer, outcome after therapy has 
been shown to be dependent on tumor stage, serum PSA and Gleason score (grade) 
[D’Amico 1998, Freedland 2004, Kattan 1998]. Because of this association, prostate 
cancer can be stratified as: very low risk (<5% risk of disease relapse after primary therapy, 
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 therapy, criteria; cT1-2, Gleason <6, PSA < 10 ng/mL); intermediate risk 
(25% risk of disease relapse after primary therapy, criteria; cT2b-2c, Gleason 7, PSA 10-
20 ng/mL) and high risk (>50% risk of disease relapse after primary therapy, criteria; cT3a, 
Gleason 8-10, PSA > 20 ng/mL) [NCCN guidelines 2014]. Thus a consistent observation 
that long-term survival is possible in patients with very low risk and low risk prostate 
cancer managed in a conservative fashion (i.e., active surveillance) is an important aspect 
when counseling patients. Despite this information, many patients with very low risk or 
low risk prostate cancer are reluctant to only surveil their prostate cancer. Thus a unique 
opportunity exist to incorporate a therapeutic option, with minimal side effects, into the 
armamentarium of physicians caring for patients with very low risk and low risk prostate 
cancer.   
 
The optimal treatment strategy for very low risk and low risk prostate cancer must be one 
that is endorsed by patients and physicians, and results in little or no compromise in long 
term, disease specific survival. The rare progression of very low risk and low risk prostate 
cancer along with its high prevalence, long latency, significant morbidity associated with 
radical therapy, provide the most opportunistic and promising approach for evaluating 
nutritional agents for their cancer inhibition properties. A promising strategy, which will 
be the focus of this proposal, will be the administration of fruit extracts of Noni (Morinda 
citrifolia).   
 
STUDY DRUG 
 
Noni Extract 
Noni (Morinda citrifolia) is included in the listings of traditional medicines of Native 
Hawaiians, other Pacific Islanders, and Asian populations, and has been used to treat 
various diseases for centuries [McClatchey, 2002]. Morinda citrifolia has been found 
previously to have a significant antioxidant activity. Present-day commercially available 
Noni is reported to be composed of over 140 chemical components, including flavonoids, 
coumadins, anthraquinones, and iridoid glycosides. Three compounds: asperulosidic acid 
(an iridoid glycoside), damnacanthal (an anthraquinone) and scopoletin (a coumadin), have 


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in vitro cellular/molecular effects possibly relevant to the inhibition of cancer development 
and progression. Asperuloside is reported to suppress tumor-promoting phorbal ester 
(TPA) - or epidermal growth factor (EGF)-induced cell transformation and associated 
activating protein-1 (AP-1) transcription factor activity [Liu & Bode et al., 2001]. 
Damnacanthal, which has strong tyrosine kinase-inhibitory effects, stimulates ultraviolet-
induced apoptosis in ultraviolet-resistant human UVr-1 cells and has been shown to induce 
normal phenotypes in ras-transformed cells [Hiwasa, Arase, Chen, Kita, Umezawa, Ito, & 
Suzuki, 1999]. Scopoletin has antiproliferative effects and can induce apoptosis of human 
androgen-independent prostate cancer, PC-3 cells [Liu & Zhang et al., 2001].  
 
Clinical Experience: Noni Extracts and Cancer  
In a phase I study involving 51 patients with advanced cancers enrolled at seven dose levels 
of Noni extract, the maximum tolerated dose was six capsules four times daily (12 g). 
Although no dose-limiting adverse events were found, seven of eight patients at the next 
level (14 g), withdrew due to the challenges of ingesting so many capsules. Furthermore, 
there was no evidence to indicate an optimal therapeutic dose or dosing interval [Issell, 
2008]. In a study in which ~6-8,000 mg of Noni extract was consumed daily, a significant 
reduction in systemic inflammatory markers were noted [Akihisha, 2007].  Evidence from 
these clinical trials, as well as the preclinical data on Noni, attest to the safety (i.e., there 
was no known toxicity) and efficacy of modulating key cellular and molecular pathways 
that could be involved in prostate cancer progression, thus a confirmatory Phase II clinical 
trial using Noni extract (6,000 mg/day) is the logical next step. Note - there was no evidence 
that Noni could accelerate tumor growth. 
 
 
PATIENT ENROLLMENT CRITERIA  
 
The criteria for inclusion or exclusion of study participants.   
 
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 
 


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4. No evidence of extraprostatic disease on pelvic MRI 
 
5. No baseline PT/PTT abnormalities, coagulopathies, or who are on any blood 
thinners.  
 
6. ECOG performance status 0−2 (Appendix A) 
    
7. Participants must have normal organ and marrow function as demonstrated by the 
following parameters being: 
a. complete blood count with differential (CBC 𝑐 diff ) - no clinically 
significant findings 
b. 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 first noni dose (Appendix B) 
 
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 


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arrhythmia, or any psychological, familial, sociological or other concomitant 
condition that would not allow adequate compliance with the study protocol 
 
8. 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. 
 
9. Participation in any other interventional study or use of any other investigational 
agents within 30 days prior to study entry 
 
Inclusion of Women and Minorities 
Members of all races and ethnic groups are eligible for this trial. Since this is an 
investigation targeting men with prostate cancer, women are not eligible for the study. 
 
Recruitment Plan 
Men who were diagnosed with very low risk or low risk prostate cancer, confirmed by 
Oncotype Dx Prostate Cancer Test, within the past12 months will be invited to participate 
in this trial. After signing an informed consent form patients will be screened for eligibility. 
UHCC will advertise in local newspapers and community organizations to widen the 
recruitment/catchment areas. Working with community physicians and oncologists is the 
most direct and effective approach, and we will target the primary care physicians and 
urologists as our primary source to recruit subjects, including racial/ethnic minorities, for 
this clinical trial.   
 
TREATMENT PLAN 
 
Dose Regimen and Dose Groups 
This is a phase II study of Noni extract in prostate cancer. Intervention will be administered 
on an outpatient basis. Drug will be dispensed by clinical research staff at each of the 
participating investigational sites and self-administered by the participants. Subjects 
participating in the study will be receiving a total daily dose of 6,000 mg/day (4 capsules 
with breakfast, 4 capsules with lunch and 4 capsules with dinner). Six bottles each 
containing 60 capsules will be dispensed to each participant upon enrollment. Then 12 
bottles (at 30-day visit) and 18 bottles (at 3, 6 and 9 month visits) will be dispensed to each 
participant. Timing of next study visit schedule will be taken into consideration when drug 
is dispensed to ensure an adequate supply of drug until next visit. On the day of a study 
visit, capsules should be taken within 4 hours of visit and blood draw for required lab work.  
If the patient is scheduled to come in the afternoon, dose should be taken with lunch.     
 
Study drug administration will continue from the time of enrollment until the time of repeat 
biopsy (12 month), disease progression or until off study (see CRITERIA FOR 
EVALUATION AND ENDPOINT DEFINITION). The planned/maximum duration of 


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treatment is one year. A total of 72 bottles of study drug (4,320 capsules) will be distributed 
per subject over the 12-month treatment period.  
 
Contraindications 
Noni is contraindicated in subjects who are hypersensitive to Noni products or any of the 
inactive ingredients found in the drug product capsules.  
 
Concomitant Medications 
During study participation, subjects may not consume any additional Noni extract. Subjects 
consuming the equivalent of an additional 1,000 mg of Noni extract will be considered 
noncompliant, and will have the study requirements re-explained to them up to two 
separate visits. Persistent non-compliance for 6 months may result in removing the subject 
from study.  
 
Participants may not take anticoagulants, such as heparin, or Coumadin or steroid 
hormones or medications, which have known impact on PSA. If a subject begins taking 
these medications after being enrolled, they will be withdrawn, taken off study drug and 
replaced.  
 
A list of supplements and medications to avoid is provided in Appendix B.   
 
All medications (prescription and over-the-counter), vitamin and mineral supplements, 
nutritional supplements and/or tea consumption by the participant following signing of the 
informed consent will be documented on the concomitant medication CRF and will 
include: start and stop date, dose and route of administration, and indication. Medications 
taken for a procedure (e.g., biopsy) will also be documented. 
 
Dose Modifications 
Subjects will be assessed clinically for adverse events during screening, prior to 
enrollment, at one month during intervention, quarterly during intervention, and at the end 
of intervention. Blood will be drawn at each of these study visits to assess for any adverse 
events. Any adverse events occurring during the investigation will be managed according 
to standard medical practice.  
 
AEs requiring dose suspension or permanent discontinuation of Noni extract are listed in 
the table below. Following any LFT elevation or INR increase, study drug will be withheld 
(grade 1) or permanently discontinued (grade ≥2), and liver function and PT/PTT 
monitored weekly until resolution to normal. Study drug may be resumed when laboratory 
values return to within reference range and will continue to be monitored weekly for 4 
consecutive weeks. Study drug will also be permanently discontinued for grade 3 and 4 
AEs, unless clearly not related to therapy. For grade 3-4 AEs not related to Noni extract, 


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we will suspend the study drug, and notify the site investigator and study PI.  Noni extract 
may be reintroduced if AE resolves within 3 weeks.  
 
Adverse events affecting LFT and/or PT/PTT levels will be monitored weekly until AE 
resolves. There are no reductions in the Noni extract dose; if AEs occur that require 
suspension of drug administration, the dose will remain the same once treatment resumes. 
Subjects who have had an interruption of intake of more than 30 calendar days may be 
withdrawn from the study at the discretion of the investigator. Subjects who have an 
unresolved AE at the time of withdrawal from study treatment will continue to be followed 
until resolution of the event, if possible. If an AE persists for more than 30 days after a 
subject goes off study, the subject will be referred to his personal physician.  
 
 


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Rules for Dose Suspension and Discontinuation  
  
Event1 
Action 
Grade 1 LFT2 elevation  
Suspend study drug; notify site investigator and study PI. 
Perform at least weekly LFTs until recovery to normal; 
study drug may be reintroduced if recovery occurs ≤2 
weeks after drug discontinuation, with approval of the 
study PI and site investigator. After reintroducing drug, 
perform at least weekly LFTs. Any elevation of LFTs after 
drug 
discontinuation 
will 
results 
in 
permanent 
discontinuation of drug. 
Grade ≥2 LFT elevation  
Permanently 
discontinue 
study 
drug; 
notify 
site 
investigator and study PI. Monitor at least weekly until 
recovery to normal. 
Grade 1 Prothrombin Time prolongation 
or 
INR increase 
Suspend study drug; notify site investigator and study PI. 
Perform at least weekly PT/PTTs until recovery to normal; 
study drug may be reintroduced if recovery occurs ≤2 
weeks after drug discontinuation, with approval of the 
study PI and site investigator. After reintroducing drug, 
perform at least weekly PT/PTTs. Any prolongation of 
PT/PTTs after drug discontinuation will results in 
permanent discontinuation of drug. 
Grade ≥2  PT prolongation 
or 
Grade ≥2 INR increase 
Permanently 
discontinue 
study 
drug; 
notify 
site 
investigator and study PI. Monitor at least weekly until 
recovery to normal. 
Bleeding of the mouth and gums, easy bleeding 
or bruising, frequent nosebleeds 
Suspend study agent until event resolves. If study drug is 
reintroduced and AE returns, permanently discontinue 
study drug. 
Grade 1 AE not related to liver function AND 
lasting less than four weeks, regardless of drug 
attribution 
No suspension required; capture AE information 
according to standard procedures. 
Grade 2 AE not related to liver function AND 
not related to therapy 
No suspension required; capture AE information 
according to standard procedures. 
Grade 1 AE that persist for greater than 4 
weeks AND related to therapy 
Suspend study agent until event resolves. If study drug is 
reintroduced and AE returns, permanently discontinue 
study drug. 
Grade 2 AE AND related to therapy 
Suspend study drug; notify site investigator and study PI. 
Study drug may be reintroduces if AE resolves within 2 
weeks. If study drug is reintroduced and AE returns, 
permanently discontinue study drug. 
Grade 3 or 4 AE AND not related to therapy 
Suspend study drug; notify site investigator and study PI.  
Noni extract may be reintroduced if AE resolves within 3 
weeks and with approval of the site investigator. 
Grade 3 or 4 AE AND related to therapy 
Permanently 
discontinue 
study 
drug; 
notify 
site 
investigator and study PI. 
Development of clinical evidence of disease 
progression 
Permanently 
discontinue 
study 
drug; 
notify 
site 
investigator and study PI. 
1AEs classified as unlikely, possibly, probably or definitely related to drug are to be considered related to therapy when assessing 
drug attribution for dose modification.  


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2Tests used to monitor liver function include: albumin, total and direct bilirubin, alkaline phosphatase, AST, ALT, total protein 
and PT/PTT 
 
Replacement 
All participants that meet the following criteria will be replaced: 
• Patients who discontinue treatment before completing 12 months of the study treatment 
for reasons other than progression of disease. 
• Patients that are enrolled but do not receive any study treatment. 
• Patients who were unable or unwilling to be in compliance with study requirements or 
were discontinued from study treatment in the judgment of the Principal Investigator. 
• Patients for whom paired biopsies are not available for evaluation and endpoint 
assessments. 
 
Adherence/Compliance 
During study participation, subjects will be asked to: self-administer the study medication; 
avoid consumption of additional Noni and complete daily drug logs to record study agent 
intake.  Subjects are expected to: maintain ≥85% compliance with study agent intake; 
comply with dietary, medication and supplement restrictions; and complete drug logs to 
the best of their ability. Subjects will be interviewed at the quarterly clinic visits, and pill 
counts will be performed to verify compliance with study requirements. Subjects 
discovered not to be complying with study requirements will have the requirements re-
explained to them up to two separate visits. Persistent non-compliance for 6 months could 
result in removing the subject from study. 
 
Plasma scopoletin, by will be measured with HPLC-EC at baseline, months 6, 9, and at the 
end of intervention as an objective marker of compliance and to correlate changes in plasma 
scopoletin levels to changes in clinical, biochemical and molecular targets. 
 
PHARMACEUTICAL INFORMATION 
 
Noni  
Noni study drug is supplied through an agreement with Healing Noni (Hilo, HI). The Noni 
plant is a small evergreen tree that grows along Hawaii’s beaches and in forest areas up to 
1,300 feet. The plant has a straight trunk, large, bright green and elliptical leaves, white 
tubular flowers and distinct, ovid, “grenade-like” yellow fruit. The fruit can grow to 12 cm 
or more and has a lumpy surface covered by polygonal-shaped sections. Its seeds are 
triangular shaped and reddish brown. To manufacture Noni extract, a proprietary technique 
to dehydrate and concentrate the Noni fruit into powder was developed. Once dried, the 
final product contains of over 140 chemical components, including flavonoids, coumadins, 
anthraquinones, and iridoid glycosides. It has been used for centuries by the Hawaiians to 
treat heart problems, diabetes, high blood pressure, arthritis, and other degenerative 
ailments.  
 


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The investigational product to be used in the proposed clinical investigation is a white, 
opaque, size 1 hard capsule containing 500 mg of Noni extract per capsule. Noni capsules 
are manufactured, stored, distributed, and evaluated for stability. Inactive excipients in 
capsules include microcrystalline cellulose NF, croscarmellose sodium NF, colloidal 
silicon dioxide NF, and magnesium stearate NF. Capsules are packaged in high-density 
polyethylene (HDPE) containers with child-resistant closures, and stored under controlled 
room temperature conditions.  
 
Rationale for Dose Selection and Administration  
Although no dose-limiting adverse events were found in the phase I clinical trial previously 
performed at UH Cancer Center, seven of eight patients at the next level (14 g), withdrew 
due to the challenges of ingesting so many capsules. Furthermore, there was no evidence 
to indicate an optimal therapeutic dose or dosing interval. In a study in which ~6-8,000 mg 
of Noni extract was consumed daily, a significant reduction in systemic inflammatory 
markers were noted.  Evidence from these clinical trials, as well as the preclinical data on 
Noni, attest to the safety and efficacy of modulating key cellular and molecular pathways 
that could be involved in prostate cancer progression, thus we propose to administer 6,000 
mg/day of Noni.  
 
Availability 
Noni capsule (500 mg) is an investigational agent supplied by agreement with Healing 
Noni.  
 
Drug Accountability 
The UHCC Central Drug Storage department is responsible for supplying the 
investigator(s)/institution(s) with the investigational product. The PI, or a responsible party 
designated by the investigator, will maintain a careful record of receipt, disposition, and 
return of all study drugs on the Investigational Agent Accountability Record. All study 
drug supplies will be kept in a locked, limited access area. The study drug will not be used 
outside the context of the protocol. Under no circumstances will the investigator or other 
site personnel supply study drug to other investigators, patients, or clinics, or allow supplies 
to be used other than directed by this protocol. Study agent will not be transferred from one 
patient to another, from one participating center to another participating center, or from 
one protocol to another. All other transfers (i.e. patient or PI moves) must be approved in 
advance by the study PI at UH Cancer Center.  
 
The investigator will maintain records documenting the receipt, use, loss or other 
disposition of the investigational product, including batch or code numbers, and account 
for the drug disposition on a subject-by-subject basis, including specific dates and 
quantities. Documentation of the subject’s participation in this clinical trial and drug and 
dosage given, must be documented in the medical and research records. Destruction of 
investigational product will be documented in accordance with UHCC SOPs. 


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Packaging and Labels 
Noni extract (500 mg) capsules are packaged with 60 capsules per bottle in 150 cc white 
HDPE bottles. Bottle labels include agent name, protocol number, dosing and storage 
instructions, required warnings for restricted, investigational use, and spaces for recording 
the subject registration. 
 
Storage 
Noni capsules will be stored in a secure location at room temperature [between 59̊ F and 
86̊ F (15–30̊ C)].  
 
Agent Destruction/Disposal 
At the completion of the study, there will be a final reconciliation of drug shipped, drug 
consumed, and drug remaining. This reconciliation will be logged on the drug 
reconciliation form, signed and dated. Any discrepancies noted will be investigated, 
resolved, and documented prior to destruction of unused study drug. Drug destroyed on 
site will be documented in the study files. 
 
REGISTRATION/ENROLLMENT/STUDY DURATION 
 
Potential subjects will be screened by the research coordinator using an Initial Assessment 
Form (Appendix C). Subjects will be provided with information about the nature of their 
current medical condition and must be willing to give consent after being informed of the 
experimental nature of therapy, alternatives, potential benefits, side-effects, risks and 
discomforts. Interested subjects who appear eligible based on information available at the 
screening will be given the opportunity to sign an Informed Consent document 
 
All subjects who sign an Informed Consent document will be assigned a registration 
number by the PI. This number will consist of a seven-digit alpha-numeric code comprised 
of: a two-digit institution code; the subject’s first and last initials; and a three digit 
sequential number assigned by the clinic site (i.e., Subject 01AZ001 would be the first 
subject registered at UH Cancer Center, 01, with initials AZ). As subjects are registered, 
demographic information and registration information will be entered into a computerized 
system for tracking purposes. 
 
After signing the informed consent and being assigned a registration number, participating 
subjects will have blood drawn for confirmation of eligibility and the original biopsy 
specimens (slides) will be collected (mandatory). If a subject is later found ineligible for 
the study based on screening blood tests or Oncotype DX analysis, the samples collected 
during screening for banking and pathology slides will be destroyed. 
 
Only men meeting all inclusion and exclusion criteria, and returning for the 


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baseline/enrollment visit will partake in the treatment phase of the study.  
 
A total of 30 men will be enrolled. Patients will receive Noni capsules (6,000 mg/day) for 
12 months of treatment intervention The accrual rate is expected to be approximately 1 to 
2 patients / month and it is expected to take about 15-30 months to accrue the 30 patients. 


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CLINICAL EVALUATIONS AND PROCEDURES 
 
Schedule of Events 
 
 
Evaluation/ 
Procedure 
 
Screening 
- 4 weeks 
Enrollment 
0 week 
1 month 
±7 days 
3 months 
±7 days 
6 months 
±7 days 
9 months 
±7 days 
12 months 
(±7 days ) or 
early 
termination 
Post-Tx 
Day 7 
Phone 
Contact 
 
Informed Consent 
Signed/Registration Number 
Assigned 
■ 
 
 
 
 
 
 
 
Demographic Questionnaire 
 
■ 
 
 
 
 
 
 
 
 
Physical Exam (weight, 
height and vital signs) 
■ 
■ 
 
 
 
 
■ 
 
AEs (Signs and Symptoms) 
 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
Concomitant Medications 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
■ 
PSA 
■1 
 
 
■ 
■ 
■ 
■ 
 
DRE 
■2 
 
 
 
  
  
■ 
 
Serum Chemistry and 
Hematology (CMP, 
CBC𝑐diff) 
■ 
 
 
■ 
■ 
■  
■ 
 
PT/PTT 
■ 
 
■ 
■ 
■ 
■ 
■ 
 
Pathology – Biopsy 
(12 core biopsies) 
■3 
 
 
 
  
 
■3 
 
Oncotype DX Prostate Test 
■3 
 
 
 
 
 
■3 
 
Pelvic MRI with contrast 
■6 
 
 
 
 
 
 
 
Compliance Check (review 
log and perform pill count) 
 
 
■ 
■ 
■ 
■ 
■ 
 
 
Collect Serum for Banking 
 
■ 
 
 
■ 
 
■ 
 
Plasma scopoletin Levels 
 
■ 
 
■ 
■ 
■ 
■ 
 
LUTS4 
 
■ 
 
■ 
■ 
■ 
■ 
 
QoL5 
 
■ 
 
■ 
■ 
■ 
■ 
 
Dispense Study Agent 
 
■ 
■ 
■ 
■ 
■ 
 
 
1PSA is not required at the screening visit if results are available from testing performed prior to the diagnostic 
biopsy, and within three months of enrollment. 
 2DRE does not need to be performed at the screening/ visit if performed by participating study sub-
investigator at time of TRUS or within six months of enrollment.   
3Original slides will be reviewed for presence of prostate cancer by a pathologist affiliated with the UHCC 
consortium.  Paraffin blocks will be sent to Genomic Health to undergo Oncotype DX Prostate Cancer Test.  
4Assessed using the AUA BPH Symptom score  
5UCLA QoL questionnaire 
6Baseline MRI repeated if >12 months 
 


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Screening visit Evaluation 
Procedures that will be performed as part of the screening/pre-enrollment process are 
described below.  
 
 Very low risk or low risk prostate cancer must be present in at least one of 8 
cores from the diagnostic biopsy. Representative slides and biopsy paraffin 
blocks from the initial biopsy are required for Oncotype DX analysis 
(mandatory) and review by pathologists affiliated with the UHCC consortium. 
 All subjects will have the study fully explained to them and will sign an informed 
consent document prior to having any invasive procedures performed. 
 A limited physical exam will be performed, including anthropometric 
measurements (height and weight) and vital signs (blood pressure). 
 Epidemiological Data: The research staff will obtain personal and physical 
characteristics, family history, history of environmental and personal 
exposures, alcohol intake, dietary and physical activity, cancer screening, 
medication use including nutritional supplements and disease outcomes as 
detailed in the Excel workbook CRF.  
 Pelvic MRI with contrast will be performed to ensure there is no extraprostatic 
disease. (Please note, MRI is not required at the screening visit if results are 
available from testing performed within twelve months of enrollment.) 
 Blood will be drawn for serum PSA, CMP, PT/PTT and CBC𝑐 diff. (Please note, 
measurement of PSA is not required at the screening visit if results are available 
from testing performed prior to the diagnostic biopsy, and within three months 
of enrollment.) 
 A DRE will be performed. (Please note, this test is not required at the screening 
visit if performed by participating study sub-investigator within six months of 
enrollment.) 
 
Enrollment 
Procedures followed during the enrollment visit are described below. Enrollment should 
take place within 4 weeks of the screening visit.  
 
 All components of eligibility will be confirmed (inclusion criteria, exclusion 
criteria). 
 Results from PSA, CMP, PT/PTT and CBC 𝑐 diff tests should be available prior to 
enrollment. 
 Subjects will be interviewed for baseline symptoms and concomitant medications. 
 LUTS score will be assessed using the AUA BPH Symptom Score Questionnaire 
(Appendix D). 
 Subjects will complete the UCLA QoL questionnaire (Appendix E). 
 Blood will be collected for baseline scopoletin measurement and banking. 


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 Six bottles (60 capsules per bottle) of study agent will be dispensed. The Study drug 
will be dispensed only to eligible patients under the supervision of the investigator 
or identified sub investigator(s). 
 The appropriate study personnel will maintain records of study drug receipt and 
dispensing. The subject will be provided with logs for recording study agent during 
the subsequent month of treatment (Appendix F).  
 
Evaluations during Study Intervention 
Months 1, 3, 6, 9: 
Procedures followed during the visits while on study intervention are described below.  
Visits should take place within ±7 days of the noted 1, 3, 6 and 9 month visits.   
 
 At each clinic visit the research staff will assess compliance (pill count) review and 
collect the study agent log (Appendix F). All symptoms experienced by the patient 
and any concomitant medications taken will be recorded on the appropriate CRF 
and clinic notes and study logs will be entered into the subject’s folder as source 
documents.  
 Serum PSA will be drawn at 3, 6 and 9 months. Note - a 30% increase in serum 
PSA over baseline PSA would trigger counseling to the patient regarding the need 
of a repeat biopsy sooner than 12 months.   
 CBC𝑐 diff and CMP will be performed at screening, 3, 6, and 9 months. PT/PTT 
will also be monitored at each study visit. If medically indicated, blood will be 
drawn for hepatic function panel.  
 Study blood will be collected at 6 and 9 months for banking and 3, 6, 9 months for 
scopoletin levels. 
 LUTS score will be assessed using the AUA BPH Symptom Score Questionnaire 
and all patients will complete the UCLA QoL questionnaire. 
 Study requirements will be reviewed with the subject. 
 Counted medication will be returned to study participants and study drug will be 
dispensed as needed, to ensure adequate supply until the next clinic visit. 
 The patient will be provided with new logs for recording study agent intake and 
reminded to note any signs and symptoms and concomitant medications. 
 
Evaluations at Completion of Study Intervention (12 months) 
The following procedures will be performed at the completion of the planned intervention 
period (12 months) or, when possible, upon early discontinuation of study agent or early 
study termination. 
 
 A limited physical exam will be performed (weight, vital signs, anthropometric 
measurements). 


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 Blood will be drawn for serum PSA, PT/PTT, CBC, CMP, plasma scopoletin 
analysis and serum banking. 
 A DRE will be performed. 
 The research staff will collect the investigational agent intake log, review signs and 
symptoms, and concomitant medications. All symptoms and concomitant 
medications will be recorded on the appropriate CRF and clinic notes and study 
logs will be entered into the subject’s folder as source documents. 
 A repeat prostate biopsy will be performed (12 core biopsy) and tissue / slides sent 
for assessment by Oncotype DX Prostate Cancer Test.  
 Finally LUTS score will be assessed using the AUA BPH Symptom Score 
Questionnaire and all patients will complete the UCLA QoL questionnaire.. 
 Remaining study medication will be collected, counted, and appropriately stored 
while awaiting destruction. 
 
Post-intervention Follow-up Period 
Subjects will be contacted by telephone 7+/-3 days after discontinuing study agent to 
capture any signs and symptoms occurring since stopping the study drug and changes to 
concomitant medications. The subject is considered off study after the repeat biopsy, other 
end-of-intervention procedures, and final telephone contact are completed. 
 
METHODS FOR CLINICAL PROCEDURES 
 
Prostate Biopsy 
Prostate tissue will be obtained and evaluated by a pathologist affiliated with the UHCC. 
Representative slides from the initial biopsy and from the biopsies obtained after treatment 
are required for analysis. At least eight (8) core biopsies will be obtained. Formalin-fixed 
paraffin-embedded prostate biopsy specimens from all patients included in this study will 
be performed at each site, where original slides will be stained with hematoxylin and eosin 
(H & E). The H&E stained sections will be evaluated by light microscopy for presence of 
prostate cancer by a pathologist with genitourinary experiences.  Then if not previously 
performed, the biopsy paraffin blocks will be sent to Genomic Health to undergo Oncotype 
DX Prostate Cancer Test.   
 
Blood Draw 
Non-fasting blood samples will be drawn following standard institutional procedures. The 
amount of blood to be collected and the types of tubes is listed under section BLOOD 
COLLECTION SCHEDULE AND PURPOSE.  
 
Anthropometric Measurements 
Anthropometric measurements such as participant’s height and weight will be performed 
at screening/pre-enrollment and post-intervention. 


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Collection of AE and Concomitant Medications Information 
All subjects on study will be asked to keep a record of any signs or symptoms and 
concomitant medications/supplements they experience once the informed consent 
document is signed. The research staff will collect the logs and review with the subject at 
each clinic visit. All signs and symptoms and concomitant medications will be recorded on 
the appropriate CRF; clinic notes and study logs will be entered into the subject’s folder as 
source documents. AEs will also be documented for abnormal results obtained during 
scheduled blood tests. All signs and symptoms and concomitant medication will be 
captured until the date the subject is terminated from the study. 
 
Demographics  
Epidemiological data as required to complete the CRF will be collected by the research 
staff and may include personal and physical characteristics, family history, history of 
environmental and personal exposures, alcohol intake, dietary and physical activity, cancer 
screening, medication use including nutritional supplements and disease. 
 
LUTS Score Assessment (AUA BPH Symptom Score questionnaire) 
LUTS will be measured at baseline, 3, 6, 9 and 12 months. LUTS represent a common 
conglomeration of symptoms (increased urinary frequency, increased urgency, hesitancy, 
reduced stream and nocturia), and have a debilitating effect on quality of life. Studies have 
demonstrated their prevalence to be as high as 90% in men aged 50−80 years old, including 
31% for moderate to severe LUTS and 59% for mild LUTS. The American Urological 
Association Symptom Score (Appendix D) for the evaluation LUTS will be used in this 
patient population. 
 
Quality of Life Assessment 
Quality of life will be measured at baseline, 3, 6, 9 and 12 months from start of intervention 
using the UCLA Prostate Cancer Index (Appendix E).  
 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION 
 
Since obtaining sufficient tissue from biopsies in this study will present a challenge, as the 
amount of tissue available may not be sufficient to conduct all the tissue biomarker studies, 
parameters for evaluation are prioritized as follows: (a) Oncotype DX Prostate Cancer Test, 
(b) angiogenesis (CD34), (c) apoptotic index, (d) Ki-67, (e) tissue procurement for 
banking. 
     
Primary Endpoint 
The primary efficacy endpoint is evaluation of the Genomic Prostate Score (GPS) after 
intervention with Noni extract. All subjects who meet eligibility criteria, have taken at least 
one dose of study medication, and have a post-treatment biopsy will be considered 


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evaluable for the primary efficacy endpoint. Tissue from prostate biopsies will be evaluated 
by a pathologist affiliated with the UHCC at screening and post-intervention with study 
agent. Representative slides from the diagnostic biopsy (at least 8 cores) and from biopsy 
specimens at 12 months post-intervention (at least 8 cores) are required for analysis. 
Biopsies will be obtained, and formalin-fixed. Paraffin-embedded prostate biopsy 
specimens from all patients included in this study will be prepared at each site, where 
original slides will be stained with H&E. Then biopsy samples will be shipped to Genomic 
Health to undergo Oncotype DX Prostate Cancer Test with the assessment of Genomic 
Prostate Score (GPS). The H&E-stained sections will be evaluated by light microscopy for 
presence of cancer, extent of cancer, grade of cancer by a centralized pathologist affiliated 
with UHCC, using uniform established standards.  
Progression of Disease 
PSA progression: 
a) PSA doubling time (DT) < 2 years, based on at least 3 separate measurements over a 
minimum of 6 months 
 
Histological progression:  
a) > 3 cores positive for prostate cancer;  
b) Gleason pattern predominant 4 or higher (i.e. Gleason 7 (4+3) or higher) in the re-
biopsy specimen of the prostate performed at 12 months as per protocol 
 
Clinical progression: 
a) more than twice increase in the product of the maximum perpendicular diameters of the 
primary lesion as measured radiographically  
b) local progression of prostate cancer requiring transurethral resection of the prostate 
c) development of ureteric obstruction 
d) radiological and/or clinical evidence of distant metastasis 
 
Secondary Endpoints 
The effects of Noni extract on serum PSA during the course of the study will be noted. 
The incidence and severity of AEs occurring during intervention will be noted. All AEs 
that are reported by the subject, detected during a visit, physical examination, or laboratory 
work-up will be recorded in the participant’s medical record and recorded on the CRF. All 
AEs that occur after study enrollment will be recorded on the AE CRF whether or not 
related to study agent. The following information will be captured for each AE: date 
reported; CTCAE Term (v 4.0); onset and resolution date; severity grade; attribution to 
study agent; whether or not the event was reported as an SAE; action taken; whether or not 
the subject dropped due to the AE; outcome; and comments. 


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Treatment related changes in angiogenesis (CD34), proliferation (Ki-67) and apoptosis 
(TUNEL) will be reported comparing initial diagnostic prostate biopsy and 12 month 
prostate biopsy provided sufficient tissue is available.   
QoL and LUTS will be noted during the course of the study.   
 
OFF DRUG CRITERIA  
Participants may stop taking study agent for the following reasons: 
 after completing the protocol-prescribed intervention 
 at the discretion of the investigator  
 AE or SAE requiring dose interruption 
 inadequate agent supply 
 noncompliance with study requirements  
 medical contraindication 
 
Off Study Criteria 
If the subject never took study medication (e.g., does not meet eligibility criteria or 
withdraws consent prior to enrollment) the only activity required to remove the subject 
from the study is to complete the Off Study CRF. If the subject was enrolled and received 
study medication, post-intervention procedures according to the schedule of events should 
be completed to the extent possible.  
Off-study criteria include: 
 not meeting enrollment (eligibility) criteria 
 the protocol intervention and any protocol-required follow-up period is 
completed  
 experiencing an AE or SAE 
 lost to follow-up 
 taking a concomitant medication 
 medical contraindication prohibiting further study participation 
 discovery of a pre-existing condition not observed at baseline eligibility 
 withdrawal of consent 
 disease progression 
 protocol non-compliance (i.e., visit schedule, dose administration, etc.) 
 at the discretion of the investigator 
 death 
 
Study Termination 
The study sponsor has the right to discontinue the study at any time.  
 
 
 


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SPECIMEN MANAGEMENT  
 
Laboratories 
Pathology: Confirmation of very low risk or low risk prostate cancer in prostate biopsy 
samples initially analyzed outside of a Hawaii Cancer Consortium institute 
will be confirmed by a pathologists associated with the Hawaii Cancer 
Consortium as standard practice. 
 
Genomic Prostate Score: Prostatic tissue (paraffin block) will be sent to Genomic 
Health and subjected to Oncotype DX Prostate Cancer Test.   
 
Serum PSA, PT/PTT, CBC and CMP: assessed by CLIA/CAP approved clinical 
laboratories 
 
Plasma scopoletin Levels: measured by Dr. Adrian Franke UH Cancer Center  
  
Collection and Handling Procedures  
 
 
Tissue Samples 
 
Prostate Cancer Pathology 
Prostate tissue will be obtained by the site surgeons. Representative slides from the initial 
biopsy and a post-intervention biopsy are required for analysis. At least eight (8) cores for 
initial diagnostic and 12 month biopsies will be obtained. Formalin-fixed, paraffin-
embedded prostate biopsy specimens from all patients included in this study will be 
prepared at each site, where original slides will be stained with H&E. The H&E stained 
sections will be evaluated by light microscopy for presence of cancer by the pathologist, 
using the uniform established standards. 
 
Paraffin embedded tissue (initial diagnosis and 12 months) will be sent to Genomic Health 
and the tissue subjected to Oncotype DX Prostate cancer Test in which a Genomic Prostate 
Score (GPS) will be rendered.  
 
Unstained slides from the above paraffin embedded blocks will be made available to Dr. 
Charles J. Rosser molecular laboratory to perform immunohistochemical staining for 
CD34 (angiogenesis), Ki-67 (proliferation) and TUNEL (apoptosis).   
 
Blood Samples 
Non-fasting blood will be collected according to the schedule shown in the table below. 
Information on processing and handling requirements for the various samples is provided 
in the sections following the table. 
 
 


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Blood Collection Schedule and Purpose: 
Tube Type: 
Speckled  
SST tube 
EDTA  
EDTA  
Speckled 
SST tube 
Sodium 
Citrate  
 
 
 
 
 
 
 
 
 
 
Total 
Amount of 
Blood 
Collected: 
~ 10 ml 
 
~ 5 ml 
~ 5 ml 
~5 ml 
~5 ml 
Processing 
Requirements: 
Serum 
Blood 
Plasma 
Serum 
 
Purpose: 
CMP1, PSA 
CBC 
Scopoletin 
levels 
Banking 
PT/PTT 
Screening 
■ 
■ 
 
 
■ 
20 ml 
Enrollment 
 
 
■ 
■ 
 
10 ml 
Month 1 
 
 
  
 
■ 
5 ml 
Month 3 
■ 
■ 
■ 
 
■ 
25 ml 
Month 6 
■ 
■ 
■ 
■ 
■ 
30 ml 
Month 9 
■ 
■ 
■ 
 
■ 
25 ml 
Month 12 
■ 
■ 
■ 
■ 
■ 
30 ml 
 
1The CMP panel includes all required tests from the hepatic function panel including direct bilirubin. 
 . 
 
PSA (Screening, Months 3, 6, 9 and 12): Approximately 5 ml of blood will be collected 
in a speckled red-top SST tube. (Please note, measurement of PSA is not required at the 
screening/pre-enrollment visit if results are available from testing performed prior to the 
diagnostic biopsy and within three months of enrollment) 
 
Comprehensive Metabolic Panel (CMP) (Screening, Months 3, 6, 9 and 12): 
Approximately 5 ml of blood will be collected in a speckled red-top SST tube. CMP 
includes glucose, BUN, creatinine, sodium, potassium, chloride, CO2, calcium, SGOT, 
SGPT, alkaline phosphatase, total bilirubin, direct bilirubin, total protein and albumin.  
 
CBC (Screening and Month 3, 6, 9 and 12): Approximately 5 ml of blood collected in 
lavender top EDTA-containing tubes will be used for CBC. Tests performed as part of the 
CBC panel include the following: WBC; RBC; HgB; HCT; MCV; MCH; MCHC; RDW; 
PLT; MPV; absolute neutrophils; absolute bands; absolute lymphs; absolute monocytes; 
absolute eosinophils; and absolute basophils. 
 
PT/PTT (Screening, Months 1, 3, 6, 9, and 12): Approximately 5 ml of blood will be 
collected in a blue-top sodium citrate containing tube to be used for PT/PTT analysis.  
 
Plasma for Scopoletin Level Analysis (Enrollment, Months 3, 6 9, and 12): 
Approximately 5 ml of blood will be collected in a lavender-top EDTA-containing tube to 


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be used for plasma scopoletin analysis. Blood will be delivered immediately to the 
Bioanalytical Core (UH Cancer Center) for assessment.   
 
Serum Banking for Future Mechanistic Studies (Enrollment, Months 6 and 12): 
Approximately 5 ml of blood will be collected in a speckled red-top SST tube and 
processed at the clinic site by standing for 20–60 minutes to clot, then spinning for 20 
minutes at 3200 rpm. The serum will be collected in separate tubes for banking at the serum 
archiving facility for future mechanistic studies with patient consent and approval from 
Institutional Review Boards. All tubes of serum will be frozen to –70ºC.   
 
Shipping Instructions 
Study samples (plasma for scopoletin and serum for banking) will be processed and 
packaged at the UHCC.  All study samples (tissue slides, paraffin blocks, plasma for 
scopoletin analysis, serum for banking) will be shipped to Dr. Rosser’s attention at UH 
Cancer Center. All samples collected will be labeled with a tough tag using a unique 
specimen number to include the (a) site number, (b) subject registration number, (c) visit 
number, (d) and specimen ID to permit computerized tracking of master and daughter 
specimens. All blood and tissue sample shipped to the UH Cancer Center for storage and 
banking will be addressed as follows:  
 
Charles Rosser, M.D., M.B.A., F.A.C.S. 
University of Hawaii Cancer Center 
701 Ilalo St. 
Rm 327 
Honolulu, HI 96813 
Contact: Janos Molnar, Ph.D. 
 
Sample Banking 
A human tissue repository consisting of prostate tissue biopsies from very low risk and low 
risk prostate cancer obtained from all subjects at baseline screening and 12 months, to 
permit the testing of hypotheses anticipated in future research for which external NIH funds 
will be sought. Serum samples will be similarly stored for future research. 
 
Sample Tracking 
All samples collected will be labeled with a unique specimen number. This information 
will be entered into an existing, customized software program for tracking. The master log, 
maintained at the UH Cancer Center, will indicate the location of each sample by storage 
box, freezer shelf, and freezer.   
 
Plasma Scopoletin Analysis 
Will be performed by HPLC-EC completed at enrollment, 3, 6, 9 and 12 months 
 


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DATA AND SAFETY MONITORING  
Adverse events will be monitored continuously through the trial. In this Phase II clinical 
trial, the local Data and Safety Monitoring Committee (DSMC) ensures that the progress 
of this protocol is monitored and that appropriate and adequate measures to monitor patient 
safety are in place. The local Data and Safety Monitoring Committee (DSMC) will monitor 
for safety and recommendations to discontinue this clinical trial. If no early stopping 
occurs, the study will end 12 months after enrollment of the final patient. The DSMC will 
meet semi-annually. In addition, serious AEs, as identified by PI will trigger the DSMC to 
immediately review any data prior to each semi-annual review. At each meeting of the 
DSMC for data monitoring, data are presented on AEs and on study outcome variables by 
the Biostatistics team. The DSMC reviews data on incidence of AEs and can recommend 
early termination if a serious imbalance were to occur and the estimated risk of harm 
appeared to warrant such action. The plan assures compliance with AE reporting and 
follow-up requirements and appropriate reporting. Data are reviewed by the DSMC every 
six months. These data include current participant accrual in the trial, baseline 
characteristics of participants, outcome data, study dropouts, and ongoing adverse event 
monitoring (tabulations of AEs). The Biostatistics team prepares the reports and then leads 
the meetings of the DSMC. Some tabulations are presented in open session; any results 
separated by intervention group are presented in closed session only to DSMC members. 
Data will be reported yearly (in closed session) to the DSMC on rates of outcome events. 
Analyses can be performed that account for varying periods of follow-up across 
participants. The DSMC will review the accumulating outcome data and evaluate the 
results in the context of results of any other trials that might be reported in the interval. 
 
REPORTING ADVERSE EVENTS (AEs)  
 
Definition: An AE is any untoward medical occurrence in a study participant. An AE does 
not necessarily have a causal relationship with the treatment or study participant. An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with participation in a study, whether 
or not related to that participation. This includes all deaths that occur while a participant is 
on a study. 
 
Reportable AEs 
All AEs that are reported by the subject, detected during a visit, physical examination, or 
laboratory work-up must be recorded in the participant’s medical record and recorded on 
the CRF. All AEs that occur after the informed consent is signed must be recorded on the 
AE CRF whether or not related to study agent. 
 
 
 
Data Elements  
 AE reported date 
 AE Verbatim Term 


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 CTCAE Term (v 4.0) 
 Event onset date and event ended date 
 Severity grade 
 Attribution to study agent (relatedness) 
 Whether or not the event was reported as a Serious AE (SAE) 
 Action taken with the study agent 
 Whether or not the subject dropped due to the event 
 Outcome of the event 
 Comments 
 
Severity of AEs 
 
 
Identify the AE using the NCI Common Terminology Criteria for AEs (CTCAE) version 
4.0. The CTCAE provides descriptive terminology and a grading scale for each AE listed. 
A copy of the CTCAE can be found at http://ctep.cancer.gov. 
 
AEs will be assessed according to the CTCAE grade associated with the AE term. AEs that 
do not have a corresponding CTCAE term will be assessed according to their impact on 
the participant’s ability to perform daily activities as follows: 
 
 
 
Grade 
 
Severity 
 
Description  
 
 
1 
 
Mild 
 
  
Barely noticeable, does not influence functioning 
 
Causing no limitations of usual activities 
2 
 
Moderate 
 
  
Makes participant uncomfortable, influences 
functioning 
 
Causing some limitations of usual activities 
3 
 
Severe 
 
  
Severe discomfort, treatment needed 
 
Severe and undesirable, causing inability to carry 
out usual activities 
4 
 
Life 
threatening 
 
  
Immediate risk of death 
 
Life threatening or disabling 
5 
Fatal 
 
Causes death of the participant 
 
 
Assessment of relationship of AE to treatment 
Relationship of the AE to study drug will be classified as one of the following:  not related, 
unlikely, possibly, probably, definitely. All AEs will be considered due to drug (AEs 
classified as unlikely, possibly, probably or definitely) unless clearly not related to therapy. 
The severity and seriousness of each AE will be assessed by the site investigator.  
  


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Follow-up of AEs 
All AEs, including lab abnormalities that in the opinion of the investigator are clinically 
significant, will be followed until resolution, if possible. If an AE persists more than 30 
days after the subject goes off study, the subject will be referred to his personal physician.  
 
SERIOUS ADVERSE EVENTS (SAEs)  
 
Definition: As those events, occurring at any dose, which meet any of the following 
criteria: 
 Results in death 
 Is life threatening (Note: the term life-threatening refers to an event in 
which the patient was at risk of death at the time of the event; it does 
not refer to an event which hypothetically might have caused death if it 
were more severe) 
 Requires inpatient hospitalization or prolongation of existing 
hospitalization 
 Results in persistent or significant disability/incapacity 
 Is a congenital abnormality/birth defect 
 Events that may not meet these criteria, but which the investigator finds 
very unusual and/or potentially serious, will also be reported in the same 
manner 
 
The PI is responsible for the reporting any unexpected fatal or life-threatening suspected 
adverse reactions to the FDA no later than 7 calendar days after initial receipt of the 
information by facsimile or email. Reporting any (1) serious, unexpected suspected adverse 
reactions, (2) findings from other clinical, animal, or in-vitro studies that suggest 
significant human risk, and (3) a clinically important increase in the rate of a serious 
suspected adverse reaction to the FDA and to all investigators no later than 15 calendar 
days after determining that the information qualifies for reporting.  
 
UH Cancer Center and all participating organizations will report SAEs to the local Data 
Safety Monitoring Committee (DSMC) according to the GCP, clinical trial regulations (21 
CFR 312.32, 312.33, and 312.64), and safety reporting guidelines.  
 
PI will contact DSMC by phone or e-mail within 24 hours of knowledge of the event. A 
SAE regardless of relatedness or expectedness will be reported to DSMC by telephone 
within 24 hours of the PI/study team becoming aware of the event. An SAE form will be 
completed by the investigator and faxed to DSMC (808-586-2984) within 48 hours. The 
investigator will keep a copy of this SAE form on file at the study site.  
 


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IRB Notification by Investigator: Reports of all SAEs (including follow-up information) 
will be submitted to the all IRBs per state and federal guidelines. Copies of each report and 
documentation of IRB notification and receipt will be kept in the Clinical Investigator’s 
binder.   
 
UH Cancer Center and all participating organizations will comply with applicable 
regulatory requirements at the participating institution related to reporting SAEs to the IRB. 
 
 
 
Follow-up of SAE 
Site staff should send follow-up reports as requested when additional information is 
available or to resolve queries. Additional information should be entered on the SAE form 
in the appropriate format. SAEs will be followed until resolved or stable, especially for 
those related to the study agent. SAEs still ongoing at the end of the study period will be 
followed up to determine the final outcome.  
 
STUDY MONITORING, AUDITING, AND INSPECTION 
 
Data Management 
The Data Management team will consist of the PI, biostatistician and Data Entry Assistant 
at UH Cancer Center. The collected data will be inputted into case report forms which will 
be uploaded into OnCore. Once the case report forms are complete, they will be transmitted 
electronically to the study biostatistician who will convert it to a SAS© (V. 9.1 or later, 
SAS® Institute, Inc., Cary, NC) database.   
 
The investigator will permit study-related monitoring, auditing, and inspection by the IRB 
and government regulatory bodies of all study-related documents (e.g., source documents, 
regulatory documents, laboratory data, data collection instruments, etc.). The investigator 
will ensure the capability for inspection of all applicable study-related facilities (e.g., 
pharmacy, diagnostic laboratory, etc.). 
 
Case Report Forms 
Participant data will be collected using protocol-specific case report forms (CRFs) that will 
be uploaded into OnCore.    
 
 
Source Documents 
Original documents (i.e., informed consent forms), patient diaries, evaluation checklists, 
laboratory reports, pharmacy dispensing records, diagnostic reports, data recorded from 
automated instruments or any clinical observation recorded in a medical record, clinic or 
physician note, or hospital record will be treated as source documentation for this clinical 
trial. Photocopies of completed case report forms are not valid source documents for this 


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clinical trial. Any data captured on the e-CRF and entered into OnCore will be supported 
by a notation in the subject’s source file.  
 
Record Retention 
Clinical records for all participants, including CRFs, all source documentation (containing 
evidence to study eligibility, history and physical findings, laboratory data, results of 
consultations, etc.), as well as IRB records and other regulatory documentation will be 
retained by the each site investigator in a secure storage facility in compliance with HIPAA, 
OHRP, FDA regulations, and ICH requirements unless the standard at the site is more 
stringent for a minimum of two years. The sponsor will be notified prior to the planned 
destruction of any materials. The records should be accessible for inspection and copying 
by authorized persons of the Food and Drug Administration. 
 
STATISTICAL CONSIDERATIONS 
 
Sample Size 
A number of methods have been developed to extract useful and robust information from 
genomic data sets. However, attention also has to be paid to the experimental design before 
the investigator completes the experiment. One of the principal limitations of previous 
molecular profiling studies is the relatively low numbers of samples analyzed.  We needed 
to estimate the sample size requirements necessary to satisfy a specified false discovery 
rate and power given various biological and experimental variations. We estimated 
variance based on previous biomarker work.  Sample size for this study was estimated 
according to equation 
where σ2 is the variance of the gene expression, Z1-α/2, Z1-β are 
the (1-α/2)th, (1-β)th quantile of the standard normal 
distribution respectively, with α being the type I error and β 
being the type II error. All signal values were log2 
transformed. Variance was calculated for each protein. The 90th percentile variance value 
(3.94) was chosen be the σ2 in equation.  In order to detect a 2-fold change in the expression 
level, (μ1 – μ0)2 in equation will be 1. We used 0.05 as the significance level. The estimated 
sample size is 30 for 80% power. Each patient will have 2 sets of genomic data (baseline 
and 12 months) collected over the course of the study to monitor a unique genomic 
signature associated with Noni extract in very low risk or low risk prostate cancer. The 
accrual rate is expected to be approximately 1 to 2 patients / month. Thus, it is expected to 
take about 15-30 months to accrue the 30 patients.  
 
Study Design/Endpoints 
The proposed clinical study is a Phase II, single arm, open label trial in men > 55 years of 
age with biopsy proven (minimum of 8 cores) very low risk or low risk prostate cancer 
(confirmed by Oncotype DX Prostate Cancer Test); a total of 30 men will be enrolled. 
Subjects will receive Noni capsules (6,000 mg/day) for 12 months. After the planned 12-


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month intervention is complete (or if a biopsy is indicated earlier), a repeat prostate biopsy 
will be performed for post-intervention endpoint measurements. The primary endpoint of 
the study is a comparison of the Genomic Prostate Score (GPS) after treatment with Noni 
extract. Furthermore, pelvic MRI with contrast will be performed and the size of any lesion 
calculated. Radiologic report of the MRI should be collected as it is a source document. 
Other endpoints include: investigating progression of prostate cancer after treatment with 
Noni extract, investigating modulation of serum PSA after treatment with Noni extract, 
reporting the tolerability of Noni extract in men with very low risk and low risk prostate 
cancer, investigating key molecular changes associated with angiogenesis, proliferation or 
apoptosis and reporting quality of life elements.    
 
ETHICAL AND REGULATORY CONSIDERATIONS 
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 312 and International Conference on Harmonization 
guidelines), applicable government regulations and Institutional research policies and 
procedures. 
 
Informed Consent 
All potential study participants will be given a copy of the IRB-approved Informed Consent 
to review. The investigator or qualified study staff will explain all aspects of the study in 
lay language and answer all questions regarding the study. If the participant decides to 
participate in the study, he will be asked to sign the Informed Consent document. The 
subject is considered enrolled in the study from the time the informed consent document is 
signed. Any and all AEs and concomitant medication taken by the study participant must 
be captured up to the time of termination from the study. The study agent(s) will not be 
released to a participant who has not signed the Informed Consent document. Subjects who 
refuse to participate or who withdraw from the study will be treated without prejudice. 
 
Participants must be provided the option to allow the use of blood samples, other body 
fluids, and tissues obtained during testing, operative procedures, or other standard medical 
practices for further research purposes. A separate signature area is required to allow 
participants to opt out of allowing tissue to be used for further research.  
 
The informed consent document must be reviewed and approved by WIRB at each 
organization at which the protocol will be implemented prior to study initiation. Any 
subsequent changes to the informed consent must be approved by WIRB prior to initiation. 
 
Confidentiality 
Information about the study subjects will be kept confidential and managed according to 
the requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Additionally, subject will not be identified by name, only subject identification 
numbers, on specimens and questionnaires. 


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Publication Plan 
Neither the complete nor any part of the results of the study carried out under this protocol, 
nor any of the information provided by the sponsor for the purposes of performing the 
study, will be published or passed on to any third party without the consent of the study 
sponsor.  Any investigator involved with this study is obligated to provide the sponsor with 
complete test results and all data derived from the study. 
 
Resource Sharing Plan 
As required by NIH rules, we will make the data collected as part of this protocol available 
to outside investigators. In order to maintain compliance with HIPAA regulations, our 
preferred method will be to execute a data sharing agreement with the requestor for a 
limited use dataset as defined by the US Department of Health and Human Services.  
 
Funding Source 
This study is financed through start-up funds from University of Hawaii Cancer Center and 
from support from Genomic Health.  
 
 
 
 


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reproduced, published, or used by other persons without prior written authorization from the study sponsor. 
 
REFERENCES 
 
Akihisa T, Matsumoto K, Tokuda H, Yasukawa K, Seino K, Nakamoto K, Kuninaga H, 
Suzuki T, Kimura Y. Anti-inflammatory and potential cancer chemopreventive 
constituents of the fruits of Morinda citrifolia (Noni). J Nat Prod. 2007 May;70(5):754-7. 
Epub 2007 May 5. 
 
D’Amico AV, Whittington R, Malkowicz SB et al. Biochemical outcome after radical 
prostatectomy, external beam radiation therapy, or interstitial radiation therapy for 
clinically localized prostate cancer. JAMA1998;280:969-974. 
 
Freedland SJ, Terris MK, Csathy GS et al. Peroperative model for predicting prostate 
specific antigen recurrence after radical prostatectomy using precent of biopsy tissue with 
cancer, biopsy Gleason grade and serum prostate specific antigen. J Urol 2004;17:2215-
2220. 
 
Hiwasa T, Arase Y, Chen Z, Kita K, Umezawa K, Ito H, Suzuki N. Stimulation of 
ultraviolet-induced apoptosis of human fibroblast UV-r 1 cells by tyrosine kinase 
inhibitors. Federation of Euro Biochem Soc Lett. 1999;444:173–176. 
 
Issell BF, Franke A, Fielding RM. Pharmacokinetic study of Noni fruit extract. J Diet 
Suppl. 2008;5(4):373-82.  
 
Kattan MW, Eastham JA, Stapleton AM, et al. A preoperative nomogram for disease 
recurrence following radical prostatectomy J Natl Cancer Inst 1998;90:766-771. 
 
Liu G, Bode A, Ma W, Sang S, Ho C, Dong Z. Two novel glycosides from the fruits of 
Morinda citrifolia (noni) inhibit AP-1 transactivation and cell transformation in the mouse 
epidermal JB6 cell line. Cancer Res. 2001;61:5749–5756. 
 
LiuX, Zhang L, Fu X, Chen K, QuianB. Effect of Scopoletin on PC-3 Cell Proliferation 
and Apoptosis. Acta Pharmacol Sin. 2001;10:929–933. 
 
McClatchey W. From Polynesian healers to health food stores: changing perspectives of 
Morinda citrifolia (Rubiaceae). Integr Cancer Ther. 2002;1(2):110–120. 
 
Prostate cancer: NCCN guidelines for prostate cancer updated. Nat Rev Urol. 2015 
Feb;12(2):63.  
 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-
Feb;65(1):5-29.  


Appendix A: Performance Status Criteria 
 
 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity. Fully active, able to carry 
on all pre-disease performance without 
restriction. 
100 
Normal, no complaints, no evidence of 
disease. 
90 
Able to carry on normal activity; minor signs 
or symptoms of disease. 
1 
Symptoms, but ambulatory. Restricted in 
physically strenuous activity, but 
ambulatory and able to carry out work of a 
light or sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
70 
Cares for self, unable to carry on normal 
activity or to do active work. 
2 
In bed <50% of the time. Ambulatory and 
capable of all self-care, but unable to carry 
out any work activities. Up and about more 
than 50% of waking hours. 
60 
Requires occasional assistance, but is able to 
care for most of his/her needs. 
50 
Requires considerable assistance and frequent 
medical care. 
3 
In bed >50% of the time. Capable of only 
limited self-care, confined to bed or chair 
more than 50% of waking hours. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. 
Death not imminent. 
4 
100% bedridden. Completely disabled. 
Cannot carry on any self-care. Totally 
confined to bed or chair. 
20 
Very sick, hospitalization indicated. Death not 
imminent. 
10 
Moribund, fatal processes progressing 
rapidly. 
5 
Dead. 
0 
Dead. 
 


 
 
 
 
 
 
Appendix B: List of Foods, Medications, and Supplements to Avoid 
 
 
Supplements to Avoid   
 
Consumption or use of any Noni or Noni-containing products 
 
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) 
 
All other herbs, vitamins, minerals, and herbal, dietary and nutritional supplements (except the 
multi-vitamin/mineral supplement provided as part of the study) should be taken under the 
discretion of the investigator.  
 
Medications to Avoid 
 
Medications, which have known impact on PSA, should not be taken while on study. These 
include: Toremifene Citrate, Finasteride, Dutasteride, Testosterone and Testosterone-like 
Supplements, Dehydroepiandrosterone (DHEA) 
 
If you have any questions about a food, supplement or medication that you are taking now or may 
be taking in the future, please do not hesitate to ask your study doctor for more information. All 
supplement and medication use should be reported to your study doctor. 
 


Appendix C: 
Phase II Clinical Study of Noni Extract in Men with Very Low Risk or Low Risk Prostate Cancer 
Initial Assessment Form 
Date      /      /          Subject Initials:       /          Year of Birth:      
YES 
NO 
QUESTION 
ACTION 
Does the subject have pathology confirmed very low risk or low 
risk prostate cancer? 
If No, STOP 
Has these biopsies been evaluated by Oncotype DX Prostate 
Cancer test or is there paraffin blocks of these biopsies available 
for the test?  
Did the subject have recent (within 6 months) prostate biopsy 
(with a minimum of 8 cores) that shows cancer? 
If No, STOP 
YES 
NO 
If the answer is “no” to any of the following questions, STOP; subject is not eligible for 
further screening at this time. (See also protocol §4.1) 
Is subject between the ages of 30-80? 
Does the subject have a PSA ≤ 10 ng/ml? 
Does the subject eat an omnivorous diet? 
Is the subject’s ECOG performance status between 0-2? 
Does the subject have normal organ and marrow function? (Per protocol §4.1) 
Is there an absence of consumption of any nutritional or herbals supplements and high dose 
antioxidants? 
Is the subject willing to not consume Noni extract? 
Is the subject willing to comply with proposed visit treatment schedule? 
Is the subject able to understand and willing to sign a written informed consent? 
YES 
NO 
STOP if response is “yes” to any of these questions; subject is not eligible for further 
screening at this time. 
Is there a prior history of prostate cancer? 
Is there a history of renal or hepatic disease including hepatitis B or C? 
Has the subject participated in any other investigational study or used any other investigational 
agents within 30 days of study entry? 
Does the subject have a history of allergic reactions attributed to Noni or other compounds of 
similar chemical? 
Has the subject taken toremifene citrate, finasteride, testosterone, dehydroepiandrosterone 
(DHEA) or other testosterone supplements within past 30 days, or dutasteride within the past 90 
days? 
Is the subject aware of having any other uncontrolled intercurrent illness (e.g., ongoing or active 
infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia)? 
Is subject eligible to continue screening?:       YES      NO  If no, specify 
Signature of Interviewer 
 Date 


AUA BPH Symptom Score Questionnaire
Patient Name: ________________________ Date of birth: ______________ Date completed _______________
Score:
1-7: Mild
8-19: Moderate
20-35: Severe
The possible total runs from 0 to 35 points with higher scores indicating more severe symptoms.
Scores less than seven are considered mild and generally do not warrant treatment.
Disclaimer: This material is provided for information purposes only and is not a substitute
for a consultation. You should consult with a urologist regarding your specific symptoms
or medical condition.
Not at All
Less than
1 in 5
Times
Less than
Half the
Time
About
Half the
Time
More than
Half the
Time
Almost
Always
Your
score
1. Over the past month,
how often have you had a
sensation of not emptying
your bladder completely
after you finished
urinating?
0
1
2
3
4
5
2. Over the past month,
how often have you had
to urinate again less than
two hours after you
finished urinating?
0
1
2
3
4
5
3. Over the past month,
how often have you
stopped and started again
several times when you
urinated?
0
1
2
3
4
5
4. Over the past month,
how often have you
found it difficult to
postpone urination?
0
1
2
3
4
5
5. Over the past month,
how often have you had a
weak urinary stream?
0
1
2
3
4
5
6. Over the past month,
how often have you had
to push or strain to begin
urination?
0
1
2
3
4
5
None
1 Time
2 Times
3 Times
4 Times
5 or More
7. Over the past month,
how many times did you
most typically get up to
urinate from the time you
went to bed at night until
the time you got up in the
morning?
0
1
2
3
4
5+
Total
Symptom
Score
Appendix D: LUTS Evaluation 


APPENDIX E: QOL 
Page 1 of 9 
 
1. The following questions are about activities you might do during a typical day. 
Does your health now limit you in these activities? If so, how much? 
 
 
 
 
 
 
(Circle 1,2, or 3 on each line) 
Yes, 
Limited 
A Lot 
Yes, 
Limited 
A little 
No, 
Not Limited 
At All 
 
a. Vigorous activities, such as running, lifting heavy objects, 
participating in strenuous sports……………………………… 
1 
2 
3 
 
b. Moderate activities, such as moving a table, pushing a 
vacuum cleaner, bowling, or playing golf…………………….. 
1 
2 
3 
 
c. Lifting or carrying groceries……………………………………. 
1 
2 
3 
 
d. Climbing several flights of stairs……………………………… 
1 
2 
3 
 
e. Climbing one flight of stairs…………………………………… 
1 
2 
3 
 
f. 
Bending, kneeling, or stooping…………………………..…… 
1 
2 
3 
 
g. Walking more than a mile……………………………............ 
1 
2 
3 
 
h. Walking several blocks…………………………………….… 
1 
2 
3 
 
i. 
Walking one block………………………………………….…. 
1 
2 
3 
 
j. 
Bathing or dressing yourself………………………………...… 
1 
2 
3 
 
 
2. During the PAST 4 WEEKS, have you had any of the following problems with your 
work or other regular daily activities as a result of your PHYSICAL HEALTH? 
(Please answer YES or NO for each question by circling 1·or 2 on each line) 
 
 
Yes 
No 
a. Cut down the amount of time you spent on work or other 
activities…………………………………………………………... 
1 
2 
b. Accomplished less than you would like……….……….…… 
1 
2 
c. Were limited in the kind of work or other activities…….……. 
1 
2 
d. Had difficulty performing the work or other activities (for 
example, it took extra effort)………………………………….... 
1 
2 
 
 
 


Page 2 of 9 
 
 
3. During the PAST 4 WEEKS, have you had any of the following problems with your 
work or other regulat daily activites as a result of any EMOTIONAL PROBLEMS, 
such as feeling depressed or anxious? 
 
 
(Please answer YES or NO for each question by circling 1 or 2 on each line) 
 
 
 
 
Yes 
No 
 
 
a. Cut down the amount of time you spent on work or other 
activities............................................................................... 
1 
2 
 
 
b. Accomplished less than you would like……………………. 
1 
2 
 
 
c. Didn't do work or other activities as carefully as usual…….. 
1 
2 
 
 
 
 
4. These questions are about how you feel and how things have been with you during 
the PAST 4 WEEKS. For each question, please give the one answer that comes 
closest to the way you have been feeling 
How much of the time during the past 4 weeks… 
 
             (Circle one number on each line) 
 
 
All  
of the 
Time 
Most  
of the 
Time 
A good Bit  
of the 
Time 
Some 
 of the 
Time 
A Little  
of the 
Time 
None  
of the 
Time 
a. Did you feel full of pep?................. 
1 
2 
3 
4 
5 
6 
b. Have you been a very nervous 
person?......................................... 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
c. Have you felt so down in the 
dumps that nothing could cheer 
you up?.......................................... 
 
 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
 
 
6 
d. Have you felt calm and peaceful?.. 
1 
2 
3 
4 
5 
6 
e. Did you have a lot of energy?........ 
1 
2 
3 
4 
5 
6 
f. 
Have you felt downhearted and 
blue?.............................................. 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
g. Did you feel worn out?................... 
1 
2 
3 
4 
5 
6 
h. Have you been a happy person?... 
1 
2 
3 
4 
5 
6 
i. 
Did you feel tired?.......................... 
1 
2 
3 
4 
5 
6 
 
5. During the past 4 weeks, how much of the time has your physical health or emotional 
problems interfered with your social activities (like visiting with friends, relatives, etc)? 
 
All of the time……. 
1 
 
 
Most of the time……. 
2 
 
 
Some of the time……. 
3 
(Circle one number) 
 
A little of the time……. 
4 
 
 
None of the time……. 
5 
 
 
 
 


Page 3 of 9 
 
6. During the past 4 weeks, to what extent has your physical health or emotional 
problems interfered with your normal social activities with family, friends, neighbors, or 
groups? 
 
Not at all……. 
1 
 
 
Slightly……. 
2 
 
 
Moderately……. 
3 
(Circle one number) 
 
Quite a bit……. 
4 
 
 
Extremely……. 
5 
 
 
7. How much bodily pain have you had during the past 4 weeks? 
 
None……. 
1 
 
 
Very mild…… 
2 
 
 
Mild……. 
3 
(Circle one number) 
 
Moderate……. 
4 
 
 
Severe……. 
5 
 
 
Very severe……. 
6 
 
 
8. During the past 4 weeks, how much did pain interfere with your normal work 
(including both work outside the home and housework)? 
 
Not at all……. 
1 
 
 
Slightly……. 
2 
 
 
Moderately……. 
3 
(Circle one number) 
 
Quite a bit……. 
4 
 
 
Extremely……. 
5 
 
 
 
9. Please choose the answer that best describes how true or false each of the 
following statements is for you. 
 
 
(Circle one number on each line) 
 
 
 
 
 
 
 
Definitely
True 
Mostly 
True 
Not Sure
Mostly 
False 
Definitely
False 
 
I seem to get sick a little easier than other
people…………………………………….… 
1 
2 
3 
4 
5 
 
I am as healthy as anyone I know………. 
1 
2 
3 
4 
5 
 
I expect my health to get worse…………. 
1 
2 
3 
4 
5 
 
My health is excellent………………………
1 
2 
3 
4 
5 
 
 
10. In general, would you say your health is: 
 
 
 
Excellent………………………….. 
1 
 
 
 
Very Good………………………… 
2 
 
 
 
Good………………………………. 
3 
(Circle one number) 
 
 
Fair………………………………… 
4 
 
 
 
Poor……………………………….. 
5 
 
 
 


Page 4 of 9 
 
11. Compared to one year ago, how would you rate your health in general now? 
 
 
Much better now than one year ago………………….……. 
1 
 
 
 
Somewhat better now than one year ago…………………. 
2 
 
 
 
About the same………………………………………………. 
3 
(Circle one number) 
 
 
Somewhat worse now than one year ago…………………. 
4 
 
 
 
Much worse now than one year ago.................................. 
5 
 
 
 
12. Below is a list of Problem Statements that describe different situations and experiences. Read 
each statement and circle the number that best describes HOW MUCH EACH STATEMENT 
APPLIES TO YOU during the PAST 4 WEEKS. 
 
 
 
(Circle one number on each line) 
 
HOW MUCH DOES IT APPLY TO YOU? 
 
 
 
 
Not At  
All 
 
A  
Little 
 
A Fair  
Amount 
 
 
Much 
 
Very 
Much 
 
a. I have difficulty bending or lifting…………………………. 
0 
1 
2 
3 
4 
 
b. I do not have the energy I used to……………………….. 
0 
1 
2 
3 
4 
 
c. I have difficulty doing household chores………………… 
0 
1 
2 
3 
4 
 
d. I have difficulty bathing, brushing my teeth, or 
grooming myself…………………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
e. I have difficulty planning activities because of the 
cancer or its treatments…………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
f. 
I cannot gain weight……………………………………….. 
0 
1 
2 
3 
4 
 
g. I find food unappealing…………………………………… 
0 
1 
2 
3 
4 
 
h. I find that cancer or its treatments interfere with my 
ability to work……………………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
i. 
I frequently have pain……………………………………... 
0 
1 
2 
3 
4 
 
j. 
I find that my clothes do not fit…………………………… 
0 
1 
2 
3 
4 
 
k. I find that doctors don't explain what they are doing to 
me…………………………………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
l. 
I have difficulty asking doctors questions………………. 
0 
1 
2 
3 
4 
 
m. I have difficulty understanding what the doctors tell me 
about the cancer or its treatments……………………….. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
n. I would like to have more control over what the doctors 
do to me…………………………………………………….. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
o. I am uncomfortable with the changes in my body……… 
0 
1 
2 
3 
4 
 
p. I frequently feel anxious…………………………………... 
0 
1 
2 
3 
4 
 
q. I have difficulty sleeping…………………………………... 
0 
1 
2 
3 
4 
 
r. 
I have difficulty concentrating…………………………….. 
0 
1 
2 
3 
4 
 
s. I have difficulty asking friends or relatives to do things 
for me……………………………………………………….. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
t. 
I have difficulty telling my friends or relatives about the 
cancer………………………………………………………. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
 
 
 
 
 
 
 


Page 5 of 9 
 
u. I find that my friends or relatives tell me I'm looking well 
when I'm not………………………………………………... 
 
0 
 
1 
 
2 
 
3 
 
4 
v. I find that my friends or relatives do not visit often 
enough……………………………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
w. I find that friends or relatives have difficulty talking with 
me about my ill ness……………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
x. I become nervous when I am waiting to see the doctor.. 
0 
1 
2 
3 
4 
 
y. I become nervous when I get my blood drawn…………. 
0 
1 
2 
3 
4 
 
z. I worry about whether the cancer is progressing…….… 
0 
1 
2 
3 
4 
 
aa. I worry about not being able to care for myself.………... 
0 
1 
2 
3 
4 
 
bb. I do not feel sexually attractive…………………………… 
0 
1 
2 
3 
4 
 
cc. I am not interested in having sex………………………… 
0 
1 
2 
3 
4 
 
dd. I sometimes don't follow my doctor's instructions……… 
0 
1 
2 
3 
4 
 
ee. I have financial problems…………………………………. 
0 
1 
2 
3 
4 
 
ff. I have insurance problems……………………………….. 
0 
1 
2 
3 
4 
 
gg. I would like to have more control over what the doctors 
do to me…………………………………………………….. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
hh. I am gaining too much weight……………………………. 
0 
1 
2 
3 
4 
 
ii. 
I have frequent episodes of diarrhea……………………. 
0 
1 
2 
3 
4 
 
jj. 
I have times when I do not have control of my bladder.. 
0 
1 
2 
3 
4 
 
13. If you have children, answer the question in this box. 
Otherwise, check here: ____ 
 
 
(Circle one number) 
HOW MUCH DOES IT APPLY TO YOU? 
 
 
Not at  
All 
A  
Little 
A Fair  
Amount 
 
Much 
Very  
Much 
 
 
I have difficulty helping my children cope with my illness………. 
0 
1 
2 
3 
4 
 
 
 
14. If you are MARRIED or in a SIGNIFICANT RELATIONSHIP, 
answer the questions in this box: 
 
 
 
 
 
(Circle one number on each line) 
HOW MUCH DOES IT APPLY TO YOU? 
 
 
Not at  
All 
A  
Little 
A Fair  
Amount 
 
Much 
Very  
Much 
 
a. My partner and I have difficulty talking about our 
feelings……………………………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
b. My partner and I have difficulty talking about wills and 
financial arrangements……………………………………. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
c. I do not feel like embracing, kissing, or caressing my 
partner………………………………………………………. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
d. My partner and I are not getting along as well as we 
usually do…………………………………………………… 
 
0 
 
1 
 
2 
 
3 
 
4 
 
e. My partner spends too much time taking care of 
me…...………………………………………………………. 
 
0 
 
1 
 
2 
 
3 
 
4 
 
f. 
I have difficulty asking my partner to take care of me…. 
0 
1 
2 
3 
4 
 
 


Page 6 of 9 
 
 
15. If you are SINGLE or NOT IN A SIGNIFICANT RELATIONSHIP, 
answer the questions in this box: 
 
 
 
 
 
(Circle one number on each line) 
HOW MUCH DOES IT APPLY TO 
YOU? 
 
 
 
Not at  
All 
A  
Little 
A Fair  
Amount 
 
Much 
Very  
Much 
 
a. I have difficulty initiating contact with potential dates….. 
0 
1 
2 
3 
4 
 
b. I have difficulty telling a date about the cancer or its 
treatments………………………………………………….. 
0 
1 
2 
3 
4 
 
 
 
URINARY FUNCTION 
 
This section is about your urinary habits. Please consider ONLY THE LAST 4 WEEKS. 
 
 
16. Over the past 4 weeks, how often have you leaked urine? 
 
 
 
Every day………………………………. 
1 
 
 
 
About once a week……………………. 
2 
 
 
 
Less than once a week……………….. 
3 
(Circle one number) 
 
 
Not at all……………………………….. 
4 
 
 
 
17. Which of the following best describes your urinary control during the last 4 weeks? 
 
 
No control whatsoever………………… 
1 
 
 
 
Frequent dribbling……………………... 
2 
(Circle one number) 
 
 
Occasional dribbling…………………... 
3 
 
 
 
Total control……………………………. 
4 
 
 
 
18. How many pads or adult diapers per day did you usually use to .control 
leakage during the last 4 weeks? 
 
 
 
3 or more pads per day……………….. 
1 
 
 
 
1-2 pads per day………………………. 
2 
 
 
 
No pads………………………………… 
3 
 
 
 
19. How big a problem, if any, has each of the following been for you? 
 
 
(Circle one number on each line) 
 
 
 
 
No  
Problem 
Very Small  
Problem 
Small  
Problem 
Moderate  
Problem 
Big  
Problem 
 
a. Dripping urine or wetting your pants 
0 
1 
2 
3 
4 
 
b. Urine leakage interfering with your 
sexual activity 
0 
1 
2 
3 
4 
 
 
 
 


Page 7 of 9 
 
 
20. Overall, how big a problem has you urinary function been for you during the last 4 weeks? 
 
No problem…………………………….. 
1 
 
 
 
Very small problem…………………… 
2 
 
 
 
Small problem……………………….. 
3 
(Circle one number) 
 
 
Moderate problem…………………… 
4 
 
 
 
Big problem……………………………. 
5 
 
 
 
BOWEL HABITS 
 
The next section is about your bowel habits and abdominal pain. 
Please consider ONLY THE LAST 4 WEEKS 
21. How often have you had rectal urgency (felt like I had to pass stool, but did 
not) during the last 4 weeks? 
 
 
 
More than once a day………………… 
1 
 
 
 
About once a day…………………….. 
2 
 
 
 
More than once a week………………. 
3 
(Circle one number) 
 
 
About once a week…………………… 
4 
 
 
 
Rarely or never……………………….. 
5 
 
 
22. How often have you had stools (bowel movements) that were loose or liquid 
(no form, watery, mushy) during the last 4 weeks? 
 
 
 
Never…………………………………… 
1 
 
 
 
Rarely…………………………………… 
2 
 
 
 
About half the time……………………. 
3 
(Circle one number) 
 
 
Usually …………………………………. 
4 
 
 
 
Always………………………………….. 
5 
 
 
23. How much distress have your bowel movements caused you during the last 4 
weeks? 
 
 
 
Severe distress……………………….. 
1 
 
 
 
Moderate distress…………………..... 
2 
(Circle one number) 
 
 
Little distress…………………………… 
3 
 
 
 
No distress…………………………….. 
4 
 
 
24. How often have you had crampy pain in your abdomen or pelvis during the last 
4 weeks? 
 
 
 
Several times a day…………………… 
1 
 
 
 
About once a day……………………… 
2 
 
 
 
Several times a week…………………. 
3 
(Circle one number) 
 
 
About once a week……………………. 
4 
 
 
 
About once this month………………… 
5 
 
 
 
Rarely or never………………………… 
6 
 
 


Page 8 of 9 
 
25. Overall, how big a problem have your bowel habits been for you during the last 
4 weeks? 
 
 
 
Big problem…………………………….. 
1 
 
 
 
Moderate problem…………………….. 
2 
 
 
 
Small problem…………………………. 
3 
(Circle one number) 
 
 
Very small problem……………………. 
4 
 
 
 
No problem…………………………….. 
5 
 
 
 
SEXUAL FUNCTION 
 
The next section is about your sexual function and sexual satisfaction. Many of the 
questions are very personal, but they will help us understand the important issues that 
you face every day. Remember, YOU NAME DOES NOT APPEAR ANYWHERE ON 
THIS SURVEY. Please answer honestly about THE LAST 4 WEEKS ONLY. 
 
 
 
26. How would you rate each of the following during the last 4 weeks? 
(Circle one number on each line) 
 
 
 
 
 
Very 
Poor 
 
Poor 
 
Fair 
 
Good 
Very 
Good 
 
a. Your level of sexual desire? …………………………………. 
1 
2 
3 
4 
5 
 
b. Your ability to have an erection? ……………………………. 
1 
2 
3 
4 
5 
 
c. Your ability to reach orgasm (climax)? …………………….. 
1 
2 
3 
4 
5 
 
 
27. How would you describe the usual QUALITY of your erections? 
 
 
None at all………………………………………………………… 
1 
 
 
Not firm enough for any sexual activity……………….............. 
2 
 
 
Firm enough for masturbation and foreplay only…………….. 
3 
(Circle one number) 
 
Firm enough for intercourse…………………………………….. 
4 
 
 
28. How would you describe the FREQUENCY of your erections? 
 
 
I NEVER had an erection when I wanted one……………....… 
1 
 
 
I had an erection LESS THAN HALF the time I wanted one… 
2 
 
 
I had an erection ABOUT HALF the time I wanted one……… 
3 
(Circle one number) 
 
I had an erection MORE THAN HALF the time I wanted one.. 
4 
 
 
I had an erection WHENEVER I wanted one……………….... 
5 
 
 
29. How often have you awakened in the morning or night with an erection? 
 
 
Never………………………………………… 
1 
 
 
Seldom (less than 25% of the time)……… 
2 
 
 
Not often (less than half the time)………… 
3 
(Circle one number) 
 
Often (more than half the time)…………… 
4 
 
 
Very often (more than 75% of the time)….. 
5 
 
 
 


Page 9 of 9 
 
30. During the last 4 weeks did you have vaginal or anal intercourse? 
 
No…………………………………………… 
1 
 
 
Yes, Once ………………………………… 
2 
(Circle one number) 
 
Yes, More than Once …………………….. 
3 
 
 
31. Overall, how would you rate your ability to function sexually during the last 4 
weeks? 
 
 
Very poor…………………………………… 
1 
 
 
Poor ………………………………………… 
2 
 
 
Fair ………………………………………….. 
3 
(Circle one number) 
 
Good ………………………………………… 
4 
 
 
Very good …………………………………... 
5 
 
 
32. Overall, how big a problem has your sexual function been for you during the last 
4 weeks? 
 
 
No problem…………………………………..  
1 
 
 
Very small problem………………………… 
2 
 
 
Small problem……………………………….  
3 
(Circle one number) 
 
Moderate problem………………………….. 
4 
 
 
Big problem…………………………………. 
5 
 
 
33. Overall, how satisfied are you with the treatment you received for your prostate 
cancer? 
 
 
Extremely dissatisfied……………………… 
1 
 
 
Dissatisfied………………………………….. 
2 
 
 
Uncertain……………………………………. 
3 
(Circle one number) 
 
Satisfied.…………………………………….. 
4 
 
 
Extremely satisfied ………………………… 
5 
 
 
 
THANK YOU VERY MUCH!! 


APPENDIX F  
 
 
 
MEDICATION  LOG 
 
 
 
Name 
Date of Birth 
Address 
 
SSN 
Doctor 
Doctor Phone # 
Pharmacy 
Pharmacy Phone # 
 
 
Medication 
Dosage 
Date 
Time 
Remark 
 

ICF_001.pdf: 
Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 1 of 25 
 
RESEARCH SUBJECT INFORMATION AND CONSENT FORM 
 
 
TITLE: 
Phase II Clinical Study of Noni Extract in Men with Very Low 
Risk or Low Risk Prostate Cancer 
 
PROTOCOL NO.: 
Huang 2015-1 
 
WIRB® Protocol #20151535 
 
PROTOCOL VERSION 
DATE: 
February 7, 2017 
 
SPONSOR: 
University of Hawaii Cancer Center 
 
INVESTIGATOR: 
Charles J. Rosser, M.D., M.B.A., F.A.C.S. 
 
701 Ilalo St., Rm. 327 
 
Honolulu, Hawaii 96813 
 
United States 
 
SUB- 
INVESTIGATORS: 
Jeffrey Huang, Pharm.D. 
 
STUDY-RELATED 
PHONE NUMBER(S): 
Charles J. Rosser, M.D., M.B.A., F.A.C.S. 
 
808-564-5994 
 
808-524-2575 (24 hours) 
 
 
University of Hawaii Cancer Center Clinical Trials Office 
 
808-586-2979 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 2 of 25 
 
WHO IS DOING THIS STUDY? 
 
The University of Hawaii Cancer Center is sponsoring this trial.  Your study doctor has met all 
requirements to be an investigator (researcher) for the University of Hawaii Cancer Center. 
 
WHY AM I BEING ASKED TO TAKE PART IN THIS STUDY? 
 
This is a clinical trial, a type of research study.  Your study doctor will explain the clinical trial 
to you.  Clinical trials include only people who choose to take part. Please take your time to 
make your decision about taking part.  You may have a copy of this consent to take home to 
review as you consider your decision to participate.  You may discuss your decision with your 
friends and family.  You can also discuss it with your health care team.  If you have any 
questions, you can ask your study doctor for more explanation. 
 
You are being asked to take part in a research study of men with very low risk or low risk 
prostate cancer who are undergoing active surveillance for their prostate cancer. 
 
WHAT IS THE USUAL APPROACH TO MY STAGE OF PROSTATE CANCER? 
 
Active surveillance (also called watchful waiting, expectant management or deferred treatment) 
is one way to treat very low risk or low risk prostate cancer.  This means that you may have 
doctor visits every 6 months to check your prostate and PSA (Prostate Specific Antigen).  Your 
doctor may recommend a prostate biopsy if your prostate examination or PSA show that your 
prostate cancer is getting bigger (progressing). 
 
Other therapy options to consider include radiation therapy (e.g. external beam radiotherapy or 
brachytherapy), surgery (radical prostatectomy), cryosurgical ablation, and high-intensity 
focused ultrasound (HiFU). 
 
Many factors need to be considered when deciding on your treatment. Such factors include 
family history and race, which may be contributing factors to aggressive disease. If you have a 
family history of prostate cancer, and/or are of African-American descent, more aggressive 
treatment options may be appropriate. Your study doctor will discuss all available treatment 
options with you. 
 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 3 of 25 
 
WHAT OTHER CHOICES DO I HAVE IF I DO NOT TAKE PART IN THIS STUDY? 
 
Your other choices may include: 
 
 You may choose to have the usual approach described above 
 You may choose to take part in a different study, if one is available 
 Or may choose not to be treated for cancer. 
 
Talk to your doctor about your choices before you decide if you will take part in this study. 
 
WHY IS THIS STUDY BEING DONE? 
 
The fruit of the Noni plant (scientific name is Morinda citrifolia) is used in traditional medicines 
of Native Hawaiians, other Pacific Islanders, and Asian populations, and has been used to treat 
various diseases such as heart problems, diabetes, high blood pressure, arthritis, and other 
degenerative ailments.  In this study, a Noni extract, made from the dehydrated (dried) fruit and 
concentrated into a pill form will be studied. 
 
The purpose of the study is to find out if Noni extract taken in a pill/capsule form every day for 
one year affects your prostate cancer.  The study will also look at the effect of Noni on 
laboratory tests for prostate cancer (PSA, the OncoType Prostate Score and associated genetic 
expression changes).  From questionnaires and doctor visits, the study will look at your quality 
of life, your urinary and bladder symptoms and any side effects of the Noni extract. 
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
 
About 30 men will participate in this study. 
 
WHAT ARE THE STUDY GROUPS? 
 
All participants in this study will take capsules that contain Noni extract every day for 1 year.  
There is no placebo group in this study. 
 
HOW LONG WILL I BE IN THIS STUDY? 
 
You will receive the Noni capsules for 1 year. 
 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 4 of 25 
 
WHAT TESTS AND PROCEDURES WILL I HAVE IF I TAKE PART IN THIS STUDY? 
 
Before you begin the study: 
 
If you decide to participate, you will be asked to sign this Informed Consent document.   
 
You will need to have the following examinations, tests or procedures to find out if you can be in 
the study. If you have had some of them done recently, they may not need to be repeated. This 
will be up to your study doctor.  After signing the consent, the following review of your 
condition will occur: 
 
 A review of your medical records. 
 A complete history and physical exam 
 A digital rectal exam (DRE) if not done by the study doctor within 6 months prior to 
enrollment to the study 
 A PSA (Prostate Specific Antigen) test if not done within three months of enrollment to 
the study. 
 Review of all your prescription and over the counter medications, including vitamins and 
other supplements 
 Blood tests (complete blood count and blood chemistries, including tests of your liver, 
kidney function and clotting ability, (about 4 teaspoons of blood) 
 MRI of your pelvis if not done within 12 months prior to enrollment to the study 
 Obtaining the prostate cancer tissue removed at the time of your biopsy and sending it for 
the Oncotype DX Prostate test.  The Oncotype DX Prostate test is a test that looks at the 
activity of certain genes in your prostate cancer in order to provide personalized 
information about how aggressive your cancer is. 
 
If these above items show that you qualify for the study, a research staff person will explain the 
study to you and if you still wish to join the study, you will be enrolled to the study and will be 
asked to complete the following: 
 
 Answer a questionnaire called the Lower Urinary Tracts Symptoms (LUTS) survey 
which asks questions about your current urinary function and bladder habit 
 Complete Quality of Life Questionnaires which ask questions as to how you function on 
a daily basis 
 Have your blood samples collected. (about 2 teaspoons of blood) 
 


Informed Consent for Clinical Research Protocols 
11/09/15 
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01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
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APPROVED 
 
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Page 5 of 25 
 
During the study: 
 
All participants in this study will receive the Noni extract.  There is no placebo group or placebo 
(blank capsules) used in this study.  A research staff person will give you the bottles of Noni 
capsules study. Each study capsule contains 500 mg Noni.  The study dose is 6,000 mg (12 
capsules) per day in divided doses.  You will take it as follows: 
 
 4 capsules with breakfast 
 4 capsules with lunch, and 
 4 capsules with dinner 
 
The capsules should be swallowed whole with at least ½ to 1 cup of water.  If you miss a meal, 
you may take the capsules on an empty stomach with the same amount of water.  If you miss a 
scheduled dose, do not try to take the missed capsules as a later time.  Please note the missed 
capsules in a pill diary and report it at your next office visit. 
 
From the date that you are given your first supply of study capsules, clinic visits with your study 
doctor will be at 1, 3 6, 9 and 12 months.  At each visit you will be given enough study capsules 
to last until your next visit up to month 12.  If there are no reasons to stop taking the study 
capsules, you will stop taking the study drug at the end of 1 year (12 months.) 
 
At your 1 month visit the following will be done: 
 
 Review your medical history and be asked if you had any side effects from the Noni 
 Review your prescription and over the counter medications, including vitamins and other 
supplements that you taking 
 Blood test to check your bloods clotting ability (about 1 teaspoon) 
 Do a count of any remaining Noni capsules that you have 
 Receive a new supply of Noni capsules 
 
At the 3-, 6-, 9-, and 12- months visits, the following will be done: 
 
 Review your medical history and be asked if you had any side effects from the Noni 
 Review your prescription and over the counter medications, including vitamins and other 
supplements 
 A DRE (digital rectal exam) 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 6 of 25 
 
 A PSA (Prostate Specific Antigen) test and blood tests (complete blood count and blood 
chemistries, including tests on your blood’s clotting ability, liver and kidney function 
(about 4 - 5 teaspoons of blood) 
 In addition to the above blood collected for the blood count and blood chemistries, extra 
research blood samples will be collected (about 1-4 teaspoons of blood) 
 Do the Lower Urinary Tracts Symptoms (LUTS) survey 
 Complete Quality of Life Questionnaires 
 Do a count of remaining Noni capsules that you have 
 Receive a new supply of Noni capsules (not at the 12-month visit) 
 
At the 12-month visit, these additional items will be done: 
 
 Instructed to stop taking the Noni capsules 
 Return any Noni capsules that you have left 
 Do a count of remaining Noni capsules 
 A physical examination, including height, weight, temperature, pulse and blood pressure 
 A DRE (digital rectal exam) and Prostate biopsy (see below) 
 
Prostate biopsy involves the placement of a sound-wave device into the rectum immediately next 
to the prostate gland. Using this sound-wave (ultrasound) device to look at the prostate as well as 
a guide, a hollow biopsy needle is used to remove pieces of prostate tissue from the prostate 
gland.  Prostate tissue from the biopsy will be sent to the pathology laboratory for examination 
and for the Oncotype DX Prostate test. 
 
Seven (7) days after your 12-month visit, research staff will contact you by phone and ask you 
about the prescription and over the counter medications, including vitamins and other 
supplements, and if you have any side effects from the Noni. 
 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 7 of 25 
 
The tests and procedures at each study visit are summarized in this table: 
 
Screening 
Baseline 
Month 
1 
Month 
3 
Month 
6 
Month 
9 
Month 
12 or 
Early 
Stop 
7 DAYS 
AFTER 
Signed Informed Consent 
X 
 
 
 
 
 
 
 
Demographic 
Questionnaire 
 
X 
 
 
 
 
 
 
Physical Exam  
X 
X 
 
 
 
 
X 
 
Digital Rectal Exam 
(DRE) 
X (if not 
done within 
6 months by 
study 
doctor) 
 
 
 
 
 
X 
 
Signs and 
Symptoms 
(Adverse Events) 
X 
X 
X 
X 
X 
X 
X 
X 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
PSA test 
X 
 
 
X 
X 
X 
X 
 
Blood Chemistry 
X 
 
 
X 
X 
X 
X 
 
PT/PTT 
X 
 
X 
X 
X 
X 
X 
 
Complete Blood Count 
X 
 
 
X 
X 
X 
X 
 
Oncotype Dx Prostate 
test 
X 
 
 
 
 
 
X 
 
Pelvic MRI with contrast 
X (or within 
prior 
12 
months) 
 
 
 
 
 
 
 
Compliance check (pill 
count and diary) 
 
 
X 
X 
X 
X 
X 
 
Research Blood Sample 
Collection 
 
X 
 
X 
X 
X 
X 
 
Quality of Life 
Questionnaires 
 
X 
 
X 
X 
X 
X 
 
Lower Urinary Tract 
Symptoms (LUTS) 
Questionnaires 
 
X 
 
X 
X 
X 
X 
 
Dispense Noni Capsules 
 
X 
X 
X 
X 
X 
 
 
Prostate Biopsy 
 
 
 
 
 
 
X 
 
 
 Includes history and physical, height, weight, and a digital rectal examination every 12 
months at the urologist’s discretion. 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 8 of 25 
 
WHAT RISKS CAN I EXPECT FROM TAKING PART IN THIS STUDY? 
 
If you choose to take part in this study, there is a risk that you may: 
 
 Lose time at work or home and spend more time in the hospital or doctor’s office than 
usual 
 Be asked sensitive or private questions which you normally do not discuss 
 
The treatment used in this study may affect how different parts of your body work such as your 
liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you 
know if changes occur that may affect your health. 
 
There is also a risk that you could have side effects from your participation in this study. 
 
Here are important points about side effects: 
 
 The study doctors do not know who will or will not have side effects. 
 Some side effects may go away soon, some may last a long time, or some may never go 
away. 
 Some side effects may be serious and may even result in death. 
 
Here are important points about how you and the study doctor can make side effects less of a 
problem: 
 
 Tell the study doctor if you notice or feel anything different so they can see if you are 
having a side effect 
 The study doctor may be able to treat some side effects. 
 The study doctor may adjust the study drugs to try to reduce side effects. 
 
There might be other side effects that researchers do not yet know about. If important new side 
effects are found, the study doctor will discuss these with you. 
 
What are the Risks of Noni Extract? 
 
There a few known risks from Noni extract.  In a previous study with Noni taken as capsules, 
study participants took about 2 to 3 times the dose of Noni used in this study.  The most common 
side effect was upset stomach or discomfort believed to be related to the number of Noni 
capsules that were taken for that study, which was up to 7 capsules taken 4 times a day. 
 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
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Page 9 of 25 
 
Allergic reactions can occur to the Noni extract or other ingredients used in the Noni capsules. 
Severe allergic reactions can be life threatening. 
 
If at any time, or at the time of your study visits, you report or your study doctor suspects or your 
blood tests show possible side effects from the Noni extract you may be told to stop taking the 
Noni capsules. You may be checked every week to see if it is safe for you to continue taking the 
Noni extract. If you have a serious side effect, or do not recover from any side effects with 30 
days, you may be told to discontinue the Noni capsules permanently, and may be taken off the 
study.  The study doctor and/or research staff will continue to monitor or keep in contact with 
you until side effects resolve. 
 
The risks for having your blood drawn include infection at the site of the blood draw, bruises and 
swelling, fainting and pain from the leaking of blood from the veins into the skin.  Trained staff 
and sterile tools will be used to minimize potential risks. 
 
Subjects will be assessed clinically (by history and examination) for side effects (adverse events) 
during screening, prior to enrollment, at all study visits and at the end of 1 year. Blood tests will 
be done as described previously to check for possible side effects on your blood count, liver and 
kidney function. 
 
The prostate biopsy can be uncomfortable and can cause bleeding in the urine or rectum or 
blood-tinged ejaculate (body fluid released by the prostate during sexual intercourse). There is 
also a risk of temporary inability to urinate or have infection. 
 
The MRI may mean some added discomfort for you.  In particular, you may be bothered by 
feelings of claustrophobia and by the loud banging noise during the MRI.  Temporary hearing 
loss has been reported from this loud noise.  You may be asked to wear ear protection.  At some 
time during the test, you may be asked to hold your breath for a while, which can be 
uncomfortable.  Because potential risks to a fetus from a MRI are unknown, pregnant women 
must not have a MRI. 
 
The effects of electromagnetic fields (EMF) on the human body are not well understood.  There 
is a very small possibility that this exposure from the MRI could have a bad effect such as 
causing some form of cancer.  The exposure in this study is not expected to greatly increase EMF 
risks, but the exact increase is unknown. 
 


Informed Consent for Clinical Research Protocols 
11/09/15 
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01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
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Feb 24, 2017 
 
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Page 10 of 25 
 
If your prostate cancer changes from very low risk or low risk prostate cancer you will be told 
and you and your doctor will discuss treatment recommendations.  It may be possible during the 
conduct of this study that a prostate biopsy is recommended due to changes in your PSA or 
prostate examination. 
 
Let your study doctor know of any questions you have about possible side effects.  You can ask 
the study doctor questions about side effects at any time. 
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
It is not possible to know at this time if taking Noni is better than the usual approach of 
surveillance. This study may or may not help you.  This study will help researchers learn things 
that may help people with very low or low risk prostate cancer in the future. 
 
CAN I STOP TAKING PART IN THIS STUDY? 
 
Yes, you can decide to stop at any time.  If you decide to stop for any reason, it is important to 
let the study doctor know as soon as possible. If you stop, you can decide whether or not to let 
the study doctor continue to provide your medical information to the organization running the 
study. 
 
The study doctor will tell you about new information or changes in the study that may affect 
your health or your willingness to continue in the study. 
 
The study doctor or sponsor may take you out of the study at any time without your consent for 
any reason including: 
 
 If your health changes and the study is no longer in your best interest 
 If new information becomes available 
 If you do not follow the study rules 
 If the study is stopped by the sponsor, Institutional Review Board (IRB) or Federal Drug 
Administration (FDA) 
 If you do not consent to continue in the study after being told of changes in the research 
that may affect you. 
 If you have a medical condition not observed at the time of screening and baseline tests 
that may have disqualified you 
 If your DRE and/or PSA results show possible worsening of your prostate cancer (no 
longer very low risk or low risk prostate cancer) 
 At the discretion of the investigator 


Informed Consent for Clinical Research Protocols 
11/09/15 
Huang 2015-1 
01/11/16-V2 
 
05/16/16-V3 
 
10/12/16-V4 
02/07/17-V5 
 
 
APPROVED 
 
AS MODIFIED 
 
Feb 24, 2017 
 
WIRB 
 
 
Page 11 of 25 
 
Hawai'i Cancer Consortium partners do not urge, influence, or encourage anyone who works for 
participating hospitals or the University of Hawai'i Cancer Center to take part in a research 
study.  Your participation in this study is completely voluntary.  You may withdraw from the 
study at any time and for any reason.  Your decision to not participate in the study, or a decision 
on your part to withdraw from the study, will have no affect whatsoever on your employment 
status.  You may refuse to participate or you may withdraw from the study at any time without 
penalty or prejudice. 
 
WHEN I AM FINISHED PARTICIPATING IN THIS STUDY 
 
After you have completed the study, you will continue with your usual care for prostate cancer. 
 
WHAT ARE MY RIGHTS IN THIS STUDY? 
 
Taking part in this study is your choice. No matter what decision you make, and even if your 
decision changes, there will be no penalty or loss of benefit to which you are otherwise entitled. 
You will not lose medical care or any legal rights. 
 
For questions about your rights while in this study, you may call the Western Institutional 
Review Board at 800-562-4789.  You may also contact the Principal Investigator, Charles J. 
Rosser, M.D., M.B.A., F.A.C.S. at 808-564-5994, or 808-524-2575 (24 hours), or the University 
of Hawai'i Cancer Center at 808-586-2979. 
 
WHAT ARE THE COSTS OF TAKING PART IN THIS STUDY? 
 
The study agent (Noni capsules) will be supplied at no charge while you take part in this study. 
 
The study will be billed for charges related to research (example PSA at 3 and 9 months, 
research blood draw). 
 
You and/or your health plan/insurance company will need to pay for all of the other costs of 
treating your cancer while in this study, including the cost of managing any side effects. 
Procedures that are standard of care will be billed to your insurance.  The 12 month oncotyping 
lab test will be paid for by the study.  Before you decide to be in the study, you should check 
with your health plan or insurance company to find out exactly what they will pay for. 
 
You are responsible for all co-pays and deductibles as you normally would be.  If you belong to 
a Medicare Advantage Plan, your claims while on this study will be billed to the regular 
Medicare and you may have a higher co-pay. 


Informed Consent for Clinical Research Protocols 
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01/11/16-V2 
 
05/16/16-V3 
 
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APPROVED 
 
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Page 12 of 25 
 
You may have transportation costs as part of your participation in this study. Please talk to the 
Principal Investigator or your study doctor if you need assistance with transportation costs during 
your participation in this study. Assistance may be available. 
 
WILL I BE PAID FOR BEING IN THE STUDY? 
 
You will not be paid for taking part in this study. 
 
WHAT HAPPENS IF I AM INJURED OR HURT BECAUSE I TOOK PART IN THIS 
STUDY? 
 
It is important that you tell your study doctor, or the Principal Investigator, Charles J. Rosser, 
M.D., M.B.A., F.A.C.S. if you feel that you have been injured because of taking part in this 
study, if you require treatment for any injury or illness related to procedures required by the 
study, or if you suffer side effects while in the study.  You can tell your doctor in person or call 
Dr. Charles Rosser at 808-564-5994 or 808-524-2575 (24 hours). 
 
The study has no plans to pay for medical treatment for injury. Your insurance company may not 
be willing to pay for study-related injury.  If you have no insurance, you will be responsible for 
any costs.  If you feel this injury was a result of medical error, you keep all your legal rights to 
receive payment for this even though you are in a study. You will get medical treatment if you 
are injured as a result of taking part in this study.  You and/or your health plan will be charged 
for this treatment.  If you are injured as a result of this study, you do not give up your right to 
pursue a claim through the legal system. 
 
WILL MY MEDICAL INFORMATION BE KEPT PRIVATE? 
 
Your privacy is very important to us and the researchers will make every effort to protect it. 
Your information may be given out if required by law. For example, certain states require 
doctors to report to health boards if they find a disease like tuberculosis. However, the 
researchers will do their best to make sure that any information that is released will not identify 
you.  Some of your health information, and information about your specimen, from this study 
will be kept in a central database for research.  Your name or contact information will not be put 
in the database. 
 


Informed Consent for Clinical Research Protocols 
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01/11/16-V2 
 
05/16/16-V3 
 
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Page 13 of 25 
 
There are organizations that may inspect your records. These organizations are required to make 
sure your information is kept private, unless required by law to provide information. Some of 
these organizations are: 
 
 The study sponsor 
  National Cancer Institute (NCI) 
 The Western Institutional Review Board® (WIRB®), a group of people who review the 
research study to protect your rights 
 The University of Hawaii Human Studies Program (UH IRB), the University’s review 
board 
 The Food and Drug Administration in the U.S., and government agencies in other 
countries where the study drug may be considered for approval 
 
USE AND DISCLOSURE OF YOUR HEALTH INFORMATION 
 
By signing this form you are authorizing the use and disclosure of individually identifiable 
information.  Your information will only be used/disclosed as described in this consent form and 
as permitted by state and federal laws.  If you refuse to give permission, you will not be able to 
be in this research. 
 
The purposes of releasing your protected health information are to collect the data needed to 
complete the research, to properly monitor (watch) how the study is done, and to answer research 
questions related to this study. 
 
There is no expiration date to this authorization. 
 
WHAT INFORMATION MAY BE USED AND GIVEN TO OTHERS? 
 
The study doctor will get your personal and medical information.  It includes: 
 
 Past and present medical records 
 Research records 
 Records about phone calls made as part of this research 
 Records about your study visits 
 Information obtained during this research about: 
 Physical exams 
 Laboratory, and other test results 
 Questionnaires 


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 Records about any study drug you received 
 Information about other medical conditions that may change your treatment and/or side 
effects you may have, and how these were treated 
 Long-term information about your general health status and the status of your disease 
 Future test results from tissue and/or blood samples that may be collected from you 
 Numbers or codes that will identify you such as your social security number and medical 
record number. 
 
MAY I WITHDRAW OR REVOKE (CANCEL) MY PERMISSION? 
 
Yes, but this permission will not stop automatically. 
 
If you choose not to be in the study, choose to withdraw from the study, or if you refuse to sign 
the authorization, it will not make a difference in your usual treatment, or your payment, and it 
will not change your eligibility for any health plan or health plan benefits that you are allowed. 
 
You may withdraw or take away your permission to use and disclose your health information at 
any time.  You do this by sending written notice to the study doctor.  If you withdraw your 
permission, you will not be able to stay in this study. 
 
When you withdraw your permission, no new health information identifying you will be 
gathered after that date.  Information that has already been gathered may still be used and given 
to others. 
 
WHO MAY USE AND GIVE OUT INFORMATION ABOUT YOU? 
 
By signing this consent form you authorize the following parties to use and/or disclose your 
identifiable health information collected or created for this study: 
 
 Charles J. Rosser, M.D., M.B.A., F.A.C.S. and his research staff for the purposes of 
conducting this research study 
 University of Hawaii Cancer Center 
 The Queen’s Medical Center 
 Island Urology Oahu LLC  
 Island Urology Hilo LLC 
 
Your medical records may contain information about AIDS or HIV infection, venereal disease, 
treatment for alcohol and/or drug abuse, or mental health or psychiatric services.  By signing this 
consent form, you authorize access to this information if it is in the records used by members of 
the research team. 


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Study information collected about you will be given to the sponsor.  “Sponsor” means any 
persons or companies that are working for or with the sponsor, or owned by the sponsor. 
 
It will also be given to the U.S. Food and Drug Administration (FDA).  It may be given to 
governmental agencies in other countries where the study drug may be considered for approval. 
 
Medical records which identify you and the consent form signed by you will be looked at and/or 
copied for research, quality assurance, data analysis or regulatory purposes by: 
 
 Representatives of the National Cancer Institute (NCI) 
 Federal, state and local agencies having oversight for this research, such as the Office for 
Human Research Protections in the U.S. Department of Health and Human Services, the 
Food and Drug Administration in the U.S., the National Institutes of Health, etc. 
 The University of Hawaii Human Studies Program, the University’s institutional review 
board 
 Western Institutional Review Board® (WIRB®) 
 The University of Hawaii Cancer Center 
 
Some of the persons or groups that receive your study information may not be required to 
comply with federal privacy regulations, and your information may lose its federal privacy 
protection and your information may be disclosed without your permission. 
 
ACCESS TO YOUR INFORMATION 
 
Your right to access your records that are created or obtained as a part of this research may be 
temporarily suspended for as long as the research is in progress if the access will potentially 
affect the outcome of this research study.  Your right to access will be restored as soon as this 
study is completed or when granting you access will not affect the outcome of this study. 
 
By signing this consent form, you will not give up any legal rights. 
 
WHERE CAN I GET MORE INFORMATION? 
 
You may visit the NCI Web site at http://cancer.gov/ for more information about studies or 
general information about cancer. You may also call the NCI Cancer Information Service to get 
the same information at: 1-800-4-CANCER (1-800-422-6237). 
 


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A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  This Web site will not include information that can identify you.  At 
most, the Web site will include a summary of the results.  You can search this Web site at 
any time. 
 
You will get a copy of this form.  If you want more information about this study, ask your study 
doctor. 
 
WHO CAN ANSWER MY QUESTIONS ABOUT THE STUDY? 
 
You can talk to your study doctor about any questions, complaints, or concerns you have about 
this study.  Contact your study doctor or Principal Investigator, Charles J. Rosser, M.D., M.B.A., 
F.A.C.S. at 808-564-5994, or 808-524-2575 (24 hours) for any of the following reasons: 
 
 If you have any questions about this study or your part in it, or 
 If you feel you have had a research-related injury or bad reaction to the study drug. 
 
Contact the University of Hawaii Cancer Center at 808-586-2979 for any of the following 
reasons: 
 
 If you have any questions about this study or your part in it, or 
 If you have questions, concerns or complaints about the research. 
 
If you have questions about your rights as a research subject or if you have questions, concerns, 
input, or complaints about the research, you may contact: 
 
 
Western Institutional Review Board® (WIRB®) 
 
1019 39th Avenue SE Suite 120 
 
Puyallup, WA 98374-2115 
 
Telephone: 1-800-562-4789 or 360-252-2500 
 
Email: Help@wirb.com 
 
WIRB® is a group of people who perform independent review of research. 
 
WIRB® will not be able to answer some study-specific questions, such as questions about 
appointment times.  However, you may contact WIRB® if the research staff cannot be reached 
or if you wish to talk to someone other than the research staff. 


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OPTIONAL RESEARCH STUDIES SECTION 
 
This part of the consent form is about optional studies that you can choose to take part in. You 
will not get health benefits from any of these studies. The researchers leading this optional study 
hope the results will help other people with cancer in the future. 
 
The results will not be added to your medical records, nor will you or your study doctor know 
the results. 
 
You will not be billed for these optional studies. You can still take part in the main study even if 
you say ‘no’ to any or all of these studies. If you sign up for but cannot complete any of the 
studies for any reason, you can still take part in the main study. 
 
Circle your choice of “yes” or “no” for each of the following studies. 
 
1. FUTURE CONTACT 
 
I agree to allow my study doctor, or someone approved by my study doctor, to 
contact me regarding future research involving my participation in this study. 
 
Yes 
No 
(Please circle your choice) 
 
2. MANDATORY BIOBANKING FOR POSSIBLE FUTURE STUDIES 
 
Researchers are trying to learn more about cancer, diabetes, and other health problems. Much of 
this research is done using samples from your tissue, blood, urine, or other fluids. Through these 
studies, researchers hope to find new ways to prevent, detect, treat, or cure health problems. 
 
Some of these studies may be about genes. Genes carry information about features that are found 
in you and in people who are related to you. Researchers are interested in the way that genes 
affect how your body responds to treatment. 
 
If you choose to take part in this study, the study doctor for the main study would like to collect a 
sample of tissue from your previous biopsy.  Also, if your disease progresses and you and your 
physician decide you should have a biopsy as part of your usual cancer care, the study doctor for 
the main study would like to collect a sample of tissue from that biopsy. 
 


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The researchers also ask your permission to store and use your samples and health 
information for medical research. The research that may be done is unknown at this time. 
Storing samples for future studies is called “biobanking”. The Biobank is being run by the 
University of Hawaii Cancer Center and supported by the National Cancer Institute. 
 
WHAT IS INVOLVED? 
 
If you agree to take part, here is what will happen next: 
 
1) Your tissue will be collected as described above and will be sent to the Biobank. 
2)  Your sample and some related information may be stored in the Biobank, along with 
samples and information from other people who take part. The samples will be kept 
until they are used up. 
3) Qualified researchers can submit a request to use the materials stored in the Biobanks. 
A science committee at the clinical trials organization will review each request. There 
will also be an ethics review to ensure that the request is necessary and proper. 
Researchers will not be given your name or any other information that could directly 
identify you. 
4) Neither you nor your study doctor will be notified when research will be conducted or 
given reports or other information about any research that is done using your samples. 
5) Some of your genetic and health information may be placed in central databases that 
may be public, along with information from many other people. Information that 
could directly identify you will not be included. 
 
WHAT ARE THE POSSIBLE RISKS? 
 
1) There is a risk that someone could get access to the personal information in your medical 
records or other information researchers have stored about you. 
2) There is a risk that someone could trace the information in a central database back to you. 
Even without your name or other identifiers, your genetic information is unique to you. 
The researchers believe the chance that someone will identify you is very small, but the 
risk may change in the future as people come up with new ways of tracing information. 
In some cases, this information could be used to make it harder for you to get or keep a 
job or insurance. There are laws against the misuse of genetic information, but they may 
not give full protection. There can also be a risk in knowing genetic information. New 
health information about inherited traits that might affect you or your blood relatives 
could be found during a study. The researchers believe the chance these things will 
happen is very small, but cannot promise that they will not occur. 


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3) Some states have laws to protect against genetic discrimination. A federal law called the 
Genetic Information Non-Discrimination Act, or GINA, is in effect.  This law helps to 
lower the risk of health insurance or employment discrimination.  The law does not 
include other types of misuse by life insurance, disability, or long term care insurance. To 
learn more about the GINA Law, please check the Internet or ask the study staff.  You 
may also call the Hawaii Department of Insurance at 808-586-2790 or the Hawaii Civil 
Rights Commission at 808-586-8636. Additional information about GINA is available at 
the end of this consent form. 
 
HOW WILL INFORMATION ABOUT ME BE KEPT PRIVATE? 
 
Your privacy is very important to the researchers and they will make every effort to protect it. 
Here are just a few of the steps they will take: 
 
1) When your samples are sent to the researchers, no information identifying you (such 
as your name) will be sent. Samples will be identified by a unique code only. 
2) The list that links the unique code to your name will be kept separate from your 
sample and health information. Any Biobank and University of Hawaii Cancer Center 
staff with access to the list must sign an agreement to keep your identity confidential. 
3) Researchers to whom University of Hawaii Cancer Center sends your sample and 
information will not know who you are. They must also sign an agreement that they 
will not try to find out who you are. 
4) Information that identifies you will not be given to anyone, unless required by law. 
5) If research results are published, your name and other personal information will not 
be used. 
 
WHAT ARE THE POSSIBLE BENEFITS? 
 
You will not benefit from taking part. The researchers, using the samples from you and others, 
might make discoveries that could help people in the future. 
 
ARE THERE ANY COSTS OR PAYMENTS? 
 
There are no costs to you or your insurance. You will not be paid for taking part. If any of the 
research leads to new tests, drugs, or other commercial products, you will not share in any 
profits. 
 


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WHAT IF I CHANGE MY MIND? 
 
If you decide you no longer want your samples to be used, you can call the Principal 
Investigator, Charles J. Rosser, M.D., M.B.A., F.A.C.S. at 808-564-5994, who will let the 
researchers know. Then, any sample that remains in the bank will no longer be used. Samples or 
related information that have already been given to or used by researchers will not be returned. 
 
If you decide to withdraw your specimens from the University of Hawaii Cancer Center 
Specimen Repository in the future, a written withdrawal of consent should be submitted 
through your study doctor to the Principal Investigator, Dr. Charles Rosser at University 
of Hawai'i Cancer Center, 701 Ilalo St., Rm. 327, Honolulu, HI 96813. Please designate, in 
the written withdrawal, whether you would prefer to have the specimens destroyed or 
returned to the study doctor. 
 
WHAT IF I HAVE MORE QUESTIONS? 
 
If you have questions about the use of your samples for research, contact the Principal 
Investigator, Charles J. Rosser, M.D., M.B.A., F.A.C.S. at 808-564-5994. 
 
Please circle your answer to show whether or not you would like to take part in each option: 
 
SAMPLES FOR FUTURE RESEARCH STUDIES: 
 
My samples and related information may be kept in a Biobank for use if future health 
research. 
 
 
YES 
NO 
 
 
(Please circle your choice) 


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FUTURE CONTACT 
 
I agree to be contacted by the University of Hawaii Cancer Center in the future regarding my 
participation in this study 
 
___________YES 
 
____________NO 
 
 
      (Please initial your choice) 
 
SIGNATURES 
 
I have read this consent form or had it read to me. I have discussed it with the study doctor and 
my questions have been answered. I will be given a signed copy of this form. I agree to take part 
in the main study and any additional studies where I circled ‘yes’.  
 
I authorize the use and disclosure of my health information to the parties listed in the authorization 
section of this consent for the purposes described above.  
 
By signing this consent form, I have not given up any of my legal rights. 
 
 
Subject's Name  – PRINTED  
 
 
Date 
Signature of Subject  
 
 
 
Name of Person Conducting Informed Consent - PRINTED 
 
 
Date 
Signature of Person Conducting Informed Consent 
 
 


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SPECIMEN CONSENT SUPPLEMENTAL SHEETS 
 
HOW ARE SPECIMENS USED FOR RESEARCH? 
 
WHERE DO SPECIMENS COME FROM? 
 
A specimen may be from a blood sample or from bone marrow, skin, toenails or other body 
materials.  People who are trained to handle specimens and protect donors' rights make sure that 
the highest standards of quality control are followed by University of Hawaii Cancer Center.  
Your doctor may not work for University of Hawaii Cancer Center, but has agreed to help collect 
specimens from many patients.  Many doctors across the country are helping in the same way. 
 
WHY DO PEOPLE DO RESEARCH WITH SPECIMENS? 
 
Research with specimens can help to find out more about what causes cancer, how to prevent it, 
how to treat it, and how to cure it.  Research using specimens can also answer other health 
questions.  Some of these include finding the causes of diabetes and heart disease, or finding 
genetic links to Alzheimer's. 
 
WHAT TYPE OF RESEARCH WILL BE DONE WITH MY SPECIMEN? 
 
Many different kinds of studies use specimens.  Some researchers may develop new tests to find 
diseases.  Others may develop new ways to treat or even cure diseases.  In the future, some of the 
research may help to develop new products, such as tests and drugs.  Some research looks at 
diseases that are passed on in families (called genetic research).  Research done with your 
specimen may look for genetic causes and signs of disease. 
 
HOW DO RESEARCHERS GET THE SPECIMEN? 
 
Researchers from universities, hospitals, and other health organizations conduct research using 
specimens.  They contact the University of Hawai'i Cancer Center and request samples for their 
studies.  The University of Hawai'i Cancer Center reviews the way that these studies will be 
done, and decides if any of the samples can be used. The University of Hawai'i Cancer Center 
gets the specimen and information about you from your hospital, and sends the specimen 
samples and some information about you to the researcher. The University of Hawai'i Cancer 
Center will not send your name, address, phone number, social security number or any other 
identifying information to the researcher. 
 


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WILL I FIND OUT THE RESULTS OF THE RESEARCH USING MY SPECIMEN? 
 
You will not receive the results of research done with your specimen.  This is because research 
can take a long time and must use specimen samples from many people before results are known.  
Results from research using your specimen may not be ready for many years and will not affect 
your care right now, but they may be helpful to people like you in the future. 
 
WHY DO YOU NEED INFORMATION FROM MY HEALTH RECORDS? 
 
In order to do research with your specimen, researchers may need to know some things about 
you.  (For example:  Are you male or female?  What is your race or ethnic group? How old are 
you?  Have you ever smoked?)  This helps researchers answer questions about diseases.  The 
information that will be given to the researcher may include your age, sex, race, diagnosis, 
treatments and family history.  This information is collected by your hospital from your health 
record and sent to the University of Hawaii Cancer Center.  If more information is needed, the 
University of Hawaii Cancer Center will send it to the researcher. 
 
WILL MY NAME BE ATTACHED TO THE RECORDS THAT ARE GIVEN TO THE 
RESEARCHER? 
 
No. Your name, address, phone number and anything else that could identify you will be 
removed before they go to the researcher.  The researcher will not know who you are. 
 
HOW COULD THE RECORDS BE USED IN WAYS THAT MIGHT BE HARMFUL TO 
ME? 
 
Sometimes, health records have been used against patients and their families.  For example, 
insurance companies may deny a patient insurance or employers may not hire someone with a 
certain illness (such as AIDS or cancer).  The results of genetic research may not apply only to 
you, but to your family members too.  For disease caused by gene changes, the information in 
one person's health record could be used against family members. 
 


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HOW AM I PROTECTED? 
 
The University of Hawaii Cancer Center is in charge of making sure that information about you 
is kept private.  The University of Hawaii Cancer Center will take careful steps to prevent misuse 
of records.  Your name, address, phone number and any other identifying information will be 
taken off anything associated with your specimen before it is given to the researcher.  This would 
make it very difficult for any research results to be linked to you or your family.  Also, people 
outside the research process will not have access to results about any one person which will help 
to protect your privacy. 
 
WHAT IF I HAVE MORE QUESTIONS? 
 
If you have any questions, please talk to your doctor or nurse, or call the Western Institutional 
Review Board® (WIRB®) at 1-800-562-4789. 


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THE GENETIC INFORMATION NONDISCRIMINATION ACT 
 
The Genetic Information Nondiscrimination Act (GINA) is a Federal law that prohibits 
discrimination in health coverage and employment based on genetic information.  This Federal 
law generally makes it illegal for health insurance companies, group health plans, and most 
employers to discriminate against you based on your genetic information. This law generally will 
protect you in the following ways: 
 
• Health insurance companies and group health plans may not request your genetic 
information that is obtained from research. 
• Health insurance companies or health plan administrators engaged in research may not 
use the information obtained to discriminate against you. 
• Health insurance companies and group health plans may not use your genetic 
information when making decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information from 
research when making a decision to hire, promote, or fire you or when setting the 
terms of your employment. 
 
All health insurance companies and group health plans must follow this law by May 21, 2010. 
All employers with 15 or more employees must follow this law as of November 21, 2009. 
 
Limitations (The following are not all inclusive, but the main limitations of GINA): 
 
• The law does not exclude life insurance companies from using genetic information to 
make decisions. 
• The law does not protect an individual if they already have a disease. It only protects 
an individual that has a genetic predisposition to a disease. 
 
For more detailed information regarding the provisions of GINA see: 
 
http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf