Clinical trial NCT01489813
Conditions: Bladder Cancer
Sponsor: Emory University
Start date: 2017-05-19; Completion date: 2024-08-31
Enrollment: 36 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Patients with non-invasive bladder cancer are often treated with intravesical therapy in order to prevent the recurrence of bladder cancer. Intravesical therapy can cause many lower urinary tract symptoms, which can limit the dose of therapy and therefore efficacy of treatment. There have been a number of studies that suggest a chemical found in soy beans may be able to help with these side effects. This chemical is called genistein and can be extracted and given to study subjects in pill form. In this study, the investigators would like to have patients placed into two different groups. One group would take genistein and the other group would take a placebo, a sugar pill that looks like the genistein pill. In doing this study the investigators hope to explore the findings from other studies to see if lower urinary tract symptoms are reduced and to see if recurrence rates for patients are affected by genistein. The study would take about four and a half months total.

Detailed description:
Patients who are treated with bacillus Calmette-Guerin (BCG) intravesical therapy for non-muscle invasive (TaT1) Tis superficial bladder cancer often develop adverse effects (urinary tract symptoms) which limit the dose (and therefore the efficacy) of therapy and result in poor quality of life. Genistein is a nutritional supplement with anti-inflammatory properties which might help alleviate adverse effects of intravesical therapy that are due to inflammation. Additionally, genistein also has anti-tumor and immunopotentiating properties and has been shown to have no known side effects. Our hypothesis is that genistein given together with BCG intravesical therapy will reduce its adverse effects and improve the efficacy of therapy. Patients (N=88) scheduled for intravesical therapy will be randomly assigned to take 30 mg tablets PO TID of genistein supplement (N=44) or placebo (N=44) during therapy and one month post therapy.

Arms: arm 1: Patients will be given placebo pills for 10 weeks. arm 2: 30 mg of genistein supplement by mouth three times daily (PO TID) for 10 weeks.
Interventions: intervention 1: Genistein intervention 2: Sugar pill
Intervention descriptions: intervention 1: 30 mg of genistein supplement by mouth three times daily (PO TID). intervention 2: Sugar pills will be taken by mouth three times daily (PO TID).

Protocol documents:
Prot_SAP_001.pdf: 
 
 
1 
 
Title: PHASE II RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL OF GENISTEIN IN 
REDUCING THE TOXICITY AND IMPROVING THE EFFICACY OF INTRAVESICAL THERAPY 
Study Principal Investigator: Omer Kucuk MD  
Study Sponsor:  Omer Kucuk, MD 
Study Co-Principal Investigator: Viraj Master, MD PhD 
Study Supporter: DSM Nutritional Products 
Version Date: 16 Jul 2019 
 
Schema: 
E
n
r
o
ll
m
e
n
t 
44 TaT1 Tis superficial bladder 
cancer patients scheduled to 
receive BCG intravesical therapy 
will be consented 
 
Estimated Timeline: until 44 
subjects are enrolled 
(approximately 2 years) 
R
a
n
d
o
m
iz
a
ti
o
n 
Arm 1: BCG 
intravesical 
therapy with 
placebo pills 
for 10 weeks 
(22 subjects) 
F
o
ll
o
w
-
u
p 
Arm 1: Followed-up according to 
standard after-treatment care: one-
month post-treatment appointment 
and subsequent doctor visits. 
Arm 2: BCG 
intravesical 
therapy with 
30 mg 
genistein 
supplement 
PO TID for 10 
weeks 
(22 subjects) 
Arm 2:  Followed-up according to 
standard after-treatment care: one-
month post-treatment appointment 
and subsequent doctor visits. 
Patients will take either 30 mg tablets of placebo or genistein supplement PO TID, for 6 weeks during 
BCG intravesical therapy and will continue for 4 weeks following therapy. 
 
 


 
 
2 
 
1. Abstract:   
Patients who are treated with BCG intravesical therapy for TaT1 Tis superficial bladder 
cancer often develop adverse effects (urinary tract symptoms) which limit the dose (and 
therefore the efficacy) of therapy and result in poor quality of life. Genistein is a nutritional 
supplement with anti-inflammatory properties which might help alleviate adverse effects of 
intravesical therapy that are due to inflammation. Additionally, genistein also has anti-tumor 
and immunopotentiating properties and has been shown to have no known side effects. Our 
hypothesis is that genistein given together with BCG intravesical therapy will reduce its 
adverse effects and improve the efficacy of therapy. Patients (N=44) scheduled for 
intravesical therapy will be randomly assigned to take 30 mg tablets of genistein supplement 
(N=22) or placebo (N=22) PO TID during therapy and one month post therapy.  
2. Introduction and Background: 
BCG intravesical therapy is a form of immunotherapy commonly used to prevent the 
recurrence of noninvasive bladder cancer, which occurs in approximately 50-80% of bladder 
cancer patients within 5 years. 10-20% of all superficial bladder cancer patients will progress 
beyond superficial recurrence within 5 years.  Smoking, poor diets, and large body weights 
are all potential risk factors for recurrence, but there is also a high propensity for bladder 
cancer recurrence in general due to its aggressive nature. As treatment, BCG intravesical 
therapy is instilled in the bladder using a urinary catheter.  The intravesical therapy remains 
in the bladder for about two hours until the patient urinates.  The treatment is usually once 
a week for six weeks and then repeated every 3-6 months for two years.  However, 
intravesical therapy typically causes urinary tract symptoms, such as pain, frequency, 
burning, inflammation, and bleeding in patients. Symptoms may occur after the very first 
treatment or become worse over time as therapy continues. As a result, the dose of therapy 
is often reduced so that symptoms can be treated symptomatically with antibiotics or pain 
medication. Dose reduction is generally done in 50% increments, and the decision to reduce 
the treatment dosage is often subjective based on each patient’s perception of symptoms. 
 
The isoflavone genistein (4,7,4'-trihydroxyisoflavone) is a phytoestrogen found in high levels 
in soy products and can be taken as a nutritional supplement for its antioxidant benefits and 
its estrogenic properties. The genistein supplement is sold over the counter and has less soy 
isoflavone than commonly found in many healthy diets. For comparison, an 8 ounce glass of 
soy milk has 15 mg of genistein. Studies have used up to 300 mg of genistein supplement 
daily, and it has been shown as safe, well accepted, and well tolerated with no known 
significant toxicities.  
 
Recent epidemiologic reports show that some Asian countries with high soy consumption 
have a smaller incidence of prostate carcinoma and studies suggest it might be due to the 
anticancer effects of soy. A study of 41 subjects in 2003 showed that there was a significant 
slow in the rate of PSA rise in prostate cancer patients after taking 100 mg of genistein 
supplement daily for 6 monthsi A recent study of 52 subjects in 2010 showed that the short-


 
 
3 
 
term, neoadjuvant synthetic aglycone genistein supplement was comparable to high 
soybean consumption and indicated a possible therapeutic benefit in early CaP, a borderline 
significant serum PSA reduction, and normalization of PSA in malignant prostate tumors.ii 
Genistein has been reported to have both anticancer and anti-inflammatory effects that 
may inhibit prostate cancer cell growth and metastasis, as well as an effect on decreased 
incidence of urinary, gastrointestinal, and erectile dysfunctions when 42 patients were 
given 100 mg genistein supplement daily for 6 months in conjunction to radiation.iii 
Additionally, a small pilot study of 8 children receiving chemotherapy and/or radiation were 
given 8 mg of the genistein supplement daily and findings suggest that the genistein 
supplement reduced the adverse effects of treatment while causing no side effects.iv The 
results from these studies suggest that further clinical investigation should be warranted to 
apply soy phytochemicals, as a potential prevention regimen for cancer progression . 
 
In a large prospective cohort of 2000 Chinese men, the association between dietary 
isoflavone and lower urinary tract symptoms (LUTS) were studied using standardized 
structured questionnaires.  A total of 96.2 % of subjects reported some consumption of 
genistein, glycitein, or daidzein. In ordinal multinominal logistic regression, subjects with 
dietary total isoflavone of more than 5.1 mg were significantly less likely to suffer from 
more severe LUTS.v The aforementioned studies suggest that the use of genistein in 
combination with intravesical therapy will allow for more effective treatment of bladder 
cancer. 
 
3. Investigational Product Information: 
 
This study will use the synthetic non-soy genistein supplement,  BonisteinTM .  BonisteinTM 
has been compounded into tablets named I-Cool ®.  Each I-Cool tablet contains 30 mg of 
genistein (BonisteinTM).  I-Cool ® and the corresponding placebo tablets are supplied by 
DSM Nutritional Products.  DSM Nutritional Products as the study product supplier, 
provides Certificate of Analysis to Study Sponsor.  Patients enrolled in the study will be 
receiving I-Cool ® tablets or the corresponding placebo tablets. 
 
4. Objectives: 
 
4.1 Primary objective 
The primary study endpoint is the change in severity of urinary symptoms over time as 
determined by the IPSS questionnaire score, specifically comparing the symptoms at the 
1st BCG treatment (baseline) to the symptoms at the 6th week of treatment. The 
difference in the degree of urinary symptoms between the placebo and genistein 
supplement arms will help reflect whether genistein supplement can improve the quality 
of life in BCG intravesical therapy patients. 
 
 
4.2 Secondary objective 


 
 
4 
 
a) A secondary study endpoint will be the presence of cancer and the rate of recurrence 
as determined by the 10-week biopsy or subsequent standard follow-up visits. 
 
b) A second secondary study endpoint will be the total dose of intravesical therapy 
administered over the 6 weeks of treatment. If subjects develop fewer urinary tract 
symptoms as a result of the genistein supplement, then hypothetically, intravesical 
therapy dosing would not have to be reduced as much. This will be measured by 
looking at the level of dose reduction for each treatment week and comparing it 
across the two arms. 
 
5. Study Design and Methods: 
At the pre-operative office visit before intravesical therapy, eligible patients will be screened 
and enrolled into the study by going through the consent process and signing the consent 
and HIPAA forms. Each patient will need to report all other medications so that the study 
team can assess whether certain medications might affect trial outcome. 
 
Patients will be randomized into Arm 1 (placebo) or Arm 2 (genistein supplement) at a ratio 
of 1:1 stratified by one dichotomized prognostic factor, age. The dichotomization will take 
place based on whether they are age 60 and above or whether they are age 59 and below. 
This will allow for similar age groups to be placed in each arm, so that the degree of urinary 
symptoms while receiving treatment is not skewed depending on the patient’s age. 
 
Patients are treated with intravesical therapy once a week for 6 weeks and then return to 
the office approximately four weeks later for a post-operative visit and biopsy, as is standard 
care. Study subjects will take their genistein or placebo tablets for a total of 10 weeks, which 
includes the length of their treatment, as well as the 4 weeks before the post-op visit. Each 
patient will fill out an International Prostate Symptom Score (IPSS) questionnaire at their 
baseline office visit when consented.  Patients will fill out an IPSS questionnaire at each 
subsequent intravesical therapy session and their final one-month follow-up appointment (at 
10 weeks) either in person or via phone call with a study team member. The IPSS 
questionnaire will gauge their urinary symptoms throughout their therapy and provide 
measurable symptom scores for the two arms. The biopsy at 10 weeks, as well as standard 3 
months follow-up appointments, is standard care for superficial bladder patients and will 
help determine cancer rate of recurrence. 
 
 


 
 
5 
 
 
Baseline 
BCG Week 1-6b 
10 Week c 
Placebo Arm 
• Screening 
(Physical Exam,a 
Vitals, a 
complete blood 
count and serum 
chemistry 
analyses, a Urine 
Dipstick, IPSS 
Questionnaire)  
• Enrollment 
• Randomization 
 
• Urine Dipstick, 
Interval History, Vitals, 
IPSS Questionnaire*, 
• BCG Intravesical 
Therapy 
• 6 weeks of placebo 
(30 mg, PO TID) 
• Continue taking 
placebo for remaining 
4 weeks before biopsy 
• Bladder Cystoscopy 
(Biopsy 
recommended, but 
not mandatory )  
• Urinary cytology (if 
inidicated) 
• Interval History 
• IPSS Questionnaire* 
• Physical Exam 
• Vital signs  
• Complete blood 
count and serum 
chemistry panel is 
recommended, but 
not mandatory 
 
 
Genistein 
Supplement 
Arm 
• Screening 
(Physical Exam, a 
Vitals, a 
complete blood 
count and 
serum 
chemistry 
analyses, a Urine 
Dipstick, IPSS 
Questionnaire) ,  
• Enrollment,  
• Randomization 
 
• Urine Dipstick, 
Interval History, Vitals, 
IPSS Questionnaire*, 
• BCG Intravesical 
Therapy 
• 6 weeks of genistein 
Supplement (30 mg,  
PO TID) 
• Continue taking 
genistein Supplement  
for remaining 4 weeks 
before biopsy 
 
• Bladder Biopsy 
(pathology)  
• Urinary cytology 
• Interval History 
• IPSS Questionnaire* 
• Physical Exam 
•  Vital signs 
• Complete blood 
count and serum 
chemistry panel is 
recommended, but 
not mandatory  
 
a Within 2 months before the first dose of study treatment.  
b A range of 7 days before or after the scheduled visit is allowed or per standard of care. If 
BCG treatment is interrupted or discontinued Urine Dipstick, Interval History, and Vitals may 
not be collected per standard of care.  
c A range of 2-3 weeks before or after the 10 week is allowed or per standard of care.  
*IPSS Questionnaire may be collected via phone call.  
6. Participant Selection: 
44 patients will be enrolled in the trial, with 22 subjects on each arm. Potential subjects will 
be superficial bladder cancer patients in the Department of Urology who are scheduled for 
their standard-of-care BCG intravesical therapy. 


 
 
6 
 
Inclusion Criteria:  
1. Male or female gender 
2. 18 years or older 
3. Diagnosis of superficial bladder cancer 
4. Scheduled for induction BCG intravesical therapy 
5. Willing and able to give blood sample 
6. Willing and able to fill out a pill diary to ensure compliance 
7. Willing and able to sign informed consent 
***Birth Control is not required for this study!  
Exclusion Criteria: 
1. Patients who are pregnant 
2. Diagnosis of muscle-invasive bladder cancer 
3. Unwillingness to follow study protocol and compliance procedures 
4. HIV positive or immunocompromised 
5. Receiving concurrent immunotherapy or chemotherapy 
6. Presence of concurrent second cancer (active, not history) 
7. Quality of Life:  
This study follows standard of care for all superficial bladder cancer subjects. All subjects 
will receive standard BCG intravesical therapy for six weeks and return for a one-month 
post-operative visit and biopsy. Both the control and intervention arms will receive the 
same care, other than taking the genistein supplement or placebo. While genistein 
supplement is not a standard part of treatment, it has been shown to not have any 
significant toxicities. It is expected that the subjects taking genistein supplement will have a   
better quality of life due to a possible reduction in urinary symptoms, such as hematuria, 
infection, frequency, urgency,  and retention, when compared to those subjects receiving 
standard treatment without the genistein supplement. Each patient’s perception of quality 
of life will be seen indirectly throughout the BCG treatment, as it is a supplemental question 
on the IPSS Questionnaire. 
Quality of life will be assessed for both arms during an interim analysis and stopping criteria 
will be determined on the degree of individual AEs as well as an interim analysis of both 
arms. Subjects with toxicities of Grade 3 or higher according the NCI CTCAE Version 4.0 will 
be immediately discontinued from the study pill. Additionally, the interim analysis will take 
place after 22 patients (11 on each arm) have been enrolled, treated, and biopsied. If the 
genistein supplement arm has statistically significant toxicities reported or greater degree 
of bladder cancer biopsies then we will immediately discontinue any future study 
enrollment. If the genistein supplement arm has significant Grade 3 toxicities, we will 
reduce the genistein supplement given by 1 tablet for 10 more patients, and if the toxicities 
persist after that, the study will be stopped.  


 
 
7 
 
8. Statistical Consideration: 
 
8.1 Power analysis 
We hypothesize that, at 6 weeks, the symptom score will increase by 6 (SD = 3.5) relative 
to the baseline in the placebo arm, while it will only increase by 3 (SD = 3.5) in the 
synthetic genistein supplement arm. A sample size of 20 patients in each arm can reach 
83% power to detect the hypothesized difference at the significance level of 0.05 by one-
sided Mann-Whitney test. 
 
In an effort to reach a sample size of 20 patients on each arm, we also hypothesize that 
there will be a 10% drop-out or non-compliance rate. We will accrue 44 patients, 22 
subjects on each arm, for this study with the expectation that 10% will drop out. With a 
10% drop out rate included, this would result in a total of 40 compliant patients. 
 
8.2 Statistical analysis plan 
 
8.2.1 Primary analysis 
The IPSS score change at 6-week from baseline will be calculated with 95% confidence 
interval and compared between two experiment groups through Mann-Whitney test. 
The baseline, minimum three treatment period IPSS scores, and the 10-week biopsy IPSS 
scores are required in order for the patient to be evaluable.  
 
8.2.2 Secondary analysis 
a) For the secondary end point of recurrence rate defined by 10-week biopsy, the 
Chi-squares test is used to test the rate difference between the two arms, and a 
logistic regression is needed to further adjust potential covariates, e.g. total BCG 
therapy dose. 
b) For the secondary end point of the total dose of intravesical therapy administered 
over 6 weeks, we consider the two-sample t test and/or sum rank test to test the 
difference between two arms. If genistein supplement works by reducing 
symptoms and maintaining the therapy dose, we expect to see a higher total 
therapy dose in its arm than in the placebo arm. 
c) We will also explore the change of IPSS score over time by the GEE model in 
which the repeated measurements of IPSS score are treated as outcome.  
Treatment, time, interaction between treatment and time, and intravesical 
therapy dose enter the model as predictors and time-dependent covariate. 
 
 
9. Adverse Event Reporting:   
 
According to 21 CFR 312.32, Adverse event means any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug related. A 
Serious adverse event or serious suspected adverse reaction is an adverse event or 
suspected adverse reaction is considered "serious" if, in the view of either the 


 
 
8 
 
investigator or sponsor, it results in any of the following outcomes: Death, a life-
threatening adverse event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions, or a congenital anomaly/birth defect. Important 
medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of 
such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
Adverse events will be recorded at each study visit via direct patient communication as 
well as through patient questionnaires. The severity of the AEs will be graded according 
to NCI CTCAE Version 4.0. Subjects with toxicities of Grade 3 or higher will be 
immediately discontinued from the study pill for the remainder of treatment. Any BCG 
intravesical therapy modifications will be done according to doctor analysis with an effort 
on alleviating toxicities as needed. In order to be evaluable, patients will need to receive 
at least three BCG instillations. If BCG treatment is interrupted or discontinued, only IPSS 
scores will be obtained via phone call. If a SAE occurs, we will promptly report it to our 
IRB upon discovery and follow the subject until the SAE is resolved. Adverse events will 
be reported to the IRB according to their requirements. 
 
IND safety reports will be sent to the FDA in accordance with 312.32 the FDA’s Guidance 
for Industry and Investigators: Safety Reporting Requirements for INDs and BA/BE 
studies. IND safety reports will document any aggregate adverse events, adverse 
reactions suspected adverse reactions, or serious adverse events. If the event is 
considered to be unexpected fatal or life-threatening, the IND safety report will be sent 
as soon as possible and within 7 business days of the investigator being notified. If 
necessary, the investigator will report any serious or life-threatening event initially by 
facsimile or telephone prior to formal submission. IND safety reports will also be 
submitted to the FDA if any related safety information is released from other sources. 
Any nonserious adverse events will be reported to the FDA in aggregate on an annual 
basis. 
 
 
10. Data and Safety Monitoring Plan (DSMP):  
 
Once the study has reached 50% accrual, investigators will plan to initially evaluate the 
results.  A group of physicians from the Winship Cancer Institute at Emory University will 
review the data and questionnaires to see how patients are reacting to the genistein 
supplement arm or whether there are drug compliance issues, such as failure to take the 
pills per protocol.  If the genistein supplement arm has statistically significant toxicities 
reported or greater degree of bladder cancer biopsies then we will immediately 


 
 
9 
 
discontinue any future study enrollment. If the genistein supplement arm has significant 
Grade 3 toxicities, we will reduce the genistein supplement given by 1 tablet for 10 more 
patients, and if the toxicities persist after that, the study will be stopped. 
Also, per Winship Cancer Institute’s Data Safety Monitoring Plan, their Data Safety 
Monitoring Committee will review the study conduct annually as well as monitor for 
regulatory compliance. 
 
 
11. References and Appendices 
i Soy Isoflavones in the Treatment of Prostate Cancer. Nutrition and Cancer. 2003 Nov;47(2):111-117. Hussain M, 
Banerjee M, Sarkar FH, Djuric Z, Pollak MN, Doerge D, Fontana J, Chinni S, Davis J, Forman J, Wood DP, Kucuk 
O. 
ii Efficacy and  safety of short-term genistein intervention in patients with localized prostate cancer prior to radical 
prostatectomy: a randomized, placebo-controlled, double-blind phase 2 clinical trial. Nutrition and Cancer IN 
PRESS. Lazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, Ramberg H, Moen A, Wessel N, Berg RE, 
Egge-Jacobsen W, Hammarstrom C, Svindland A, Kucuk O, Saatcioglu F, Tasken KA, Karlsen, SJ.  
iii Soy Isoflavones in Conjunction with Radiation Therapy in Patients with Prostate Cancer. Nutrition and  Cancer. 
2010 Oct;62(7):996-1000. Ahmed IU, Forman JD, Sarkar FH, Hillman GG, Heath E, Vaishampayan U, Cher ML, 
Andic F, Rossi P, Kucuk O. 
iv Soy Isoflavones Ameliorate the Adverse Effects of Chemotherapy in Children. Nutrition and Cancer. 2010 Oct; 
62(7): 1001-1005. Tacyildiz N, Ozyoruk D, Yavuz G, Unal E, Dincaslan H, Dogu F, Sahin F, Kucuk, O. 
v The association between isoflavone and lower urinary tract symptoms in elderly men. Br J Nutr. 2007 
Dec;98(6):1237-42. Wong SY, Lau WW, Leung PC, Leung JC, Woo J. 
                                                 

ICF_000.pdf: 
 
 
 
 
 
Informed Consent Form 
 
 
Phase II, Randomized, Placebo-Controlled, Clinical Trial of Genistein in Reducing 
the Toxicity and Improving the Efficacy of Intravesical Therapy 
 
NCT Number: NCT01489813 
 
 
Document IRB Approval Date: 8/07/2018 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
  
 
 
You Are Being Asked to Be in a Research Study 
 
What Is a Research Study? 
The main purpose of research studies is to gain knowledge. This knowledge may be used to 
help others. Research studies are not intended to benefit you directly, though some might.   
 
Do I Have to Do This? 
No. Being in this study is entirely your choice.  If you decide to join this study, you can 
change your mind later on and withdraw from the research study.  
 
Taking part in a study is separate from medical care. The decision to join or not join the 
research study will not affect your status as a patient.   
 
What Is This Document? 
This form is an informed consent document. It will describe the study risks, procedures, and 
any costs to you. 
 
This form is also a HIPAA Authorization document. It will describe how your health information 
will be used and by whom. 
 
Signing this form indicates you are willing to take part in the study and allow your health 
information to be used. 
 
What Should I Do Next? 
1. Read this form, or have it read to you. 
2. Make sure the study doctor or study staff explains the study to you. 
3. Ask questions (e.g., time commitment, unfamiliar words, specific procedures, etc.)  
4. If there will be medical treatment, know which parts are research and which are 
standard care. 
5. Take time to consider this, and talk about it with your family and friends. 
 
 
 
 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 1 of 11                                       Version Date: 08/02/2018 
    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017 
 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
 
Emory University and Saint Joseph’s Hospital 
Consent to be a Research Subject / HIPAA Authorization  
 
 
Title: Phase II Randomized Placebo-Controlled Clinical Trial of Genistein in Reducing the Toxicity 
and Improving the Efficacy of Intravesical Therapy  
 
Sponsor-Investigator: Omer Kucuk, MD 
 
Co-Principal Investigator: Viraj Master, MD PhD 
 
Study Supporter:  DSM Nutritional Products 
 
Introduction 
You are being asked to be in a medical research study. This form is designed to tell you everything 
you need to think about before you decide if you want to be a part of the study.  It is entirely your 
choice.  If you decide to take part, you can change your mind later on and withdraw from the 
research study. The decision to join or not join the research study will not cause you to lose any 
medical benefits.  If you decide not to take part in this study, your doctor will continue to treat you. 
 
Before making your decision: 
• Please carefully read this form or have it read to you 
• Please listen to the study doctor or study staff explain the study to you  
• Please ask questions about anything that is not clear 
 
You can take a copy of this consent form, to keep. Feel free to take your time thinking about whether 
you would like to participate. You may wish to discuss your decision with family or friends. Do not sign 
this consent form unless you have had a chance to ask questions and get answers that make sense 
to you.  By signing this form you will not give up any legal rights. 
 
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. 
 
Purpose 
The purpose of this study is to identify the risks and benefits of a taking genistein supplement, I-
Cool®, while receiving intravesical therapy to prevent the recurrence of bladder cancer.  Genistein is 
a chemical found in soy beans. 
 
Procedures 
You will be given a brief questionnaire to fill about demographic information and your urinary 
symptoms. Before your first intravesical therapy you will be randomly assigned to either receive 
genistein supplement, I-Cool® tablets or a placebo, an inactive substance. You have a 50:50 chance 
of being in either group, like the flip of a coin.  At each treatment visit you will be asked to bring in 
your pill diary and fill out a questionnaire about your urinary symptoms (either at the visit or via a 
phone call).  A month after you finish your intravesical therapy you will be asked to return to clinic 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 2 of 11                                       Version Date: 08/02/2018 
    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017 
 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
where you will have a bladder biopsy to see if the intravesical therapy was effective in stopping 
cancer from coming back in your bladder.  You will be asked to fill out the urinary symptoms 
questionnaire again as well.  Also, the research team will also look at your medical records to get 
more information about your treatment. 
 
How will my genistein supplement be provided?  
The genistein supplement that you will take will be dispensed by the pharmacy and delivered to the 
principal investigator or study team member.  The principal investigator or health care providers on 
his/her research team will provide the genistein supplement to you.  If you have questions about the 
genistein supplement, you should ask the study doctors.  
 
Risks and Discomforts  
There may be side effects from the study drug that are not known at this time.  Your condition may 
not get better, and it may even get worse, as a result of your being in this study.  Using the drug may 
involve risks that are already known, as well as risks which are currently not known.  Problems and 
side effects may occur that are not currently expected and this includes unusual, unexpected, or 
previously unreported side effects.  You should also understand that your cancer symptoms may not 
be controlled by the study drug used in this study and may even worsen.  Different types of side 
effects may occur in different people.  Therefore, it is important that you report all symptoms and side 
effects that you experience as soon as they occur, whether or not you think they are caused by the 
study drug. Since genistein reportedly has anti-inflammatory properties, it is unknown whether 
genistein may reduce the effectiveness of BCG response by decreasing the inflammation associated 
with the treatment. You will be informed as soon as possible of any new information about this study 
drug.  Additionally, this study involves answering questionnaires which should not take longer than 5 
minutes to complete.  
 
Benefits  
This study is not designed to benefit you directly.  Your urinary symptoms may improve while you are 
in this study but they may not, and they may even get worse.  This study is designed to learn more 
about how genistein supplement affects symptoms from intravesical therapy.   The study results may 
be used to help others in the future. 
 
Other Treatment Outside this Study 
You do not have to be in this study to be treated. You are free to choose not to take part. The study 
doctor will discuss these with you.  You do not have to be in this study to be treated for you condition. 
 
Medical Record 
 
If you have been an Emory and Saint Joseph’s Hospital patient before, then you already have an 
Emory and Saint Joseph’s Hospital medical record.  If you have never been an Emory and Saint 
Joseph’s Hospital patient, you do not have one.   An Emory and Saint Joseph’s Hospital medical 
record will be made for you if an Emory and Saint Joseph’s Hospital provider or facility gives you any 
services or procedures for this study.   
 
Copies of the consent form/HIPAA authorization that you sign will be put in any Emory and Saint 
Joseph’s Hospital medical record you have now or any time during the study.   
 
Emory and Saint Joseph’s Hospital may create study information about you that can help with your 
care.  For example, the results of study tests or procedures.  These study results will be put in your 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 3 of 11                                       Version Date: 08/02/2018 
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Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
Emory and Saint Joseph’s Hospital medical record. Anyone who has access to your medical records 
will be able to have access to all the study information placed there.  The confidentiality of the study 
information in your medical record will be protected by laws like the HIPAA privacy rule.  State and 
federal laws may not protect the research information from disclosure.  
 
The results of some study tests and procedures will be used only for research purposes and will not 
be placed in your medical record.  For this study, those items include: the questionnaires filled out at 
weeks 2, 6, and 10 post-operatively.  
 
Tests and procedures done at non-Emory and Saint Joseph’s Hospital places may not become part 
of your Emory and Saint Joseph’s Hospital medical record. Also, if you decide to be in this study, it is 
up to you to let your other health providers know.  
 
In Case of Injury 
If you get ill or injured from being in the study, Emory and Saint Joseph’s Hospital will help you to get 
medical treatment.   Emory and Saint Joseph’s Hospital and the sponsor have not, however, set 
aside any money to pay you or to pay for this medical treatment. The only exception is if it is proven 
that your injury or illness is directly caused by the negligence of an Emory and Saint Joseph’s 
Hospital or sponsor employee.  “Negligence” is the failure to follow a standard duty of care.  
If you become ill or injured from being in this study, your insurer will be billed for your treatment costs.  
If you do not have insurance, or if your insurer does not pay, then you will have to pay these costs.   
If you believe you have become ill or injured from this research, you should contact Dr. Omer Kucuk 
at 
 or Dr. Viraj Master at 
.You should also let any health care provider 
who treats you know that you are in a research study.  
Costs 
Emory and Saint Joseph’s Hospital will pay for the genistein supplement, I-Cool tablets, or the 
placebo but does not plan to pay for any other items or services that you may receive if you take part 
in this study.     
 
Emory and Saint Joseph’s Hospital will not pay for your regular medical care. If you have insurance, 
Emory and Saint Joseph’s Hospital will submit claims to your insurance for items and services that 
the sponsor does not cover.  Emory and Saint Joseph’s Hospital will send in only those claims for 
items and services that it reasonably believes your insurance will pay and that the sponsor has not 
paid.  
 
The actual amount that you have to pay depends on whether or not you have health insurance and 
whether or not that insurance will pay for any research study costs. Generally, insurance companies 
will not pay for items and services that are required just for a research study. Some insurance 
companies will not pay for regular medical treatment or treatment for complications if you are in a 
study.  How much you will have to pay for any co-payments, deductibles or co-insurance depends on 
your plan.  Emory and Saint Joseph’s Hospital and the sponsor will not pay for these costs.  
 
It is a good idea to contact your insurance provider and tell them you want to be in this research 
study.  Ask them what they will pay for and what they will not pay for.  You can also ask the study 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 4 of 11                                       Version Date: 08/02/2018 
    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017 
 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
team for help in figuring out what you will have to pay.  
 
If you do not have insurance, Emory and Saint Joseph’s Hospital will review your case as part of its 
program for low-income patient care.  The standard policies of that program will apply.  The program 
will figure out if you have to pay any costs for taking part in the study and what those costs will be. 
 
Withdrawal from the Study 
You have the right to leave a study at any time without penalty.   
 
For your safety, however, you should consider the study doctor’s advice about how to go off the study 
treatment.  If you leave the study before the final planned study visit, the researchers may ask you to 
have some of the final steps done.   
 
The researchers also have the right to stop your participation in this study without your consent for any 
reason, especially if they believe it is in your best interest or if you were to object to any future changes 
that may be made in the study plan. 
 
Authorization to Use and Disclose Protected Health Information 
 
The privacy of your health information is important to us.  We call your health information that 
identifies you, your “protected health information” or “PHI.”  To protect your PHI, we will follow federal 
and state privacy laws, including the Health Insurance Portability and Accountability Act and 
regulations (HIPAA).  We refer to all of these laws as the “Privacy Rules.”  Here we let you know how 
we will use and disclose your PHI for the main study and for any optional studies in which you may 
choose to participate. 
 
PHI that Will be Used/Disclosed:   
The PHI that we will use or share for the main research study includes: 
• Medical information about you including your medical history and present/past 
medications. 
• Results of exams, procedures and tests you have before and during the study. 
• Laboratory test results. 
 
Purposes for Which Your PHI Will be Used/Disclosed: 
We will use and share your PHI for the conduct and oversight of the research study.  We will use and 
share your PHI to provide you with study related treatment and for payment for such treatment.  We 
will also use and share your PHI to conduct normal business operations.  We may share your PHI 
with other people and places that help us conduct or carry out the study, such as laboratories, data 
management centers, data monitors, contract research organizations, Institutional Review Boards 
(IRBs) and other study sites. If you leave the study, we may use your PHI to determine your health, 
vital status or contact information. We will use and disclose your PHI for the administration and 
payment of any costs relating to subject injury from the study.  
 
Use and Disclosure of Your Information That is Required by Law:   
We will use and disclose your PHI when we are required to do so by law. This includes laws that 
require us to report child abuse or abuse of elderly or disabled adults. We will also comply with legal 
requests or orders that require us to disclose your PHI. These include subpoenas or court orders.   
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    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017 
 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
 
Authorization to Use PHI is Required to Participate: 
By signing this form, you give us permission to use and share your PHI as described in this 
document. You do not have to sign this form to authorize the use and disclosure of your PHI.  If you 
do not sign this form, then you may not participate in the research study or receive research-related 
treatment.  You may still receive non-research related treatment.   
 
People Who will Use/Disclose Your PHI: 
The following people and groups will use and disclose your PHI in connection with the research 
study: 
 
• The Principal Investigator and the research staff will use and disclose your PHI to 
conduct the study and give you study related treatment. 
• Emory and Saint Joseph’s Hospital may use and disclose your PHI to get payment for 
study related treatment and to run normal business operations. c 
• The Principal Investigator and research staff will share your PHI with other people and 
groups to help conduct the study or to provide oversight for the study. 
•  Dr. Omer Kucuk is the Sponsor of the study.  The Sponsor may use and disclose your 
PHI to make sure the research is done correctly and to collect and analyze the results of 
the research.  The Sponsor may disclose your PHI to other people and groups like 
study monitors to help conduct the study or to provide oversight for the study.   
• The research team and the Sponsor may use and disclose your PHI, including 
disclosure to insurance carriers to administer payment for subject injury.  
• The following people and groups will use your PHI to make sure the research is done 
correctly and safely: 
o Emory and Saint Joseph’s Hospital offices that are part of the Human Research 
Participant Protection Program and those that are involved in study 
administration and billing.  These include the Emory IRB, the Emory Research 
and Compliance Offices, and the Emory Office for Clinical Research.  
o Government agencies that regulate the research including:  Food and Drug 
Administration 
o Public health agencies. 
o Research monitors and reviewer. 
o Accreditation agencies. 
• Sometimes a Principal Investigator or other researcher moves to a different institution. If 
this happens, your PHI may be shared with that new institution and their oversight 
offices. PHI will be shared securely and under a legal agreement to ensure it continues 
to be used under the terms of this consent and HIPAA authorization. 
 
Expiration of Your Authorization 
Your PHI will be used until this research study ends. 
 
Revoking Your Authorization 
If you sign this form, at any time later you may revoke (take back) your permission to use your 
information.  If you want to do this, you must write: 
 
Dr. Omer Kucuk 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 6 of 11                                       Version Date: 08/02/2018 
    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017 
 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
1365 Clifton Road NE 
Suite B4301 
Atlanta, GA 30322 
 
OR 
 
Dr. Viraj Master 
The Emory Clinic Department of Urology 
1365 Clifton Road, Suite B 1400 
Altanta, GA 30322 
 
At that point, the researchers would not collect any more of your PHI.  But they may use or disclose 
the information you already gave them so they can follow the law, protect your safety, or make sure 
that the study was done properly and the data is correct.  If you revoke your authorization you will not 
be able to stay in the study.  
 
Other Items You Should Know about Your Privacy 
Not all people and entities are covered by the Privacy Rules.  HIPAA only applies to health care 
providers, health care payers, and health care clearinghouses.  If we disclose your information to 
people who are not covered by the Privacy Rules, including HIPAA, then your information won’t be 
protected by the Privacy Rules.  People who do not have to follow the Privacy rules can use or 
disclose your information with others without your permission if they are allowed to do so by the laws 
that cover them.   
 
To maintain the integrity of this research study, you generally will not have access to your PHI related 
to this research until the study is complete.  When the study ends, and at your request, you generally 
will have access to your PHI that we maintain in a designated record set.  A designated record set is 
data that includes medical information or billing records that your health care providers use to make 
decisions about you. If it is necessary for your health care, your health information will be provided to 
your doctor.  
 
We may remove identifying information from your PHI.  Once we do this, the remaining information 
will not be subject to the Privacy Rules.  Information without identifiers may be used or disclosed with 
other people or organizations for purposes besides this study.   
 
Contact Information 
Contact Dr. Omer Kucuk at 
 or Dr. Viraj Master at 
: 
• if you have any questions about this study or your part in it,   
• if you feel you have had a research-related injury or a bad reaction to the study drug, or 
• if you have questions, concerns or complaints about the research 
 
Contact the Emory Institutional Review Board at 
: 
• if you have questions about your rights as a research participant. 
• if you have questions, concerns or complaints about the research. 
• You may also let the IRB know about your experience as a research participant through our 
Research Participant Survey at http://www.surveymonkey.com/s/6ZDMW75. 
 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 7 of 11                                       Version Date: 08/02/2018 
    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017 
 


Study No.: IRB00050273 
Emory University IRB 
IRB use only 
Document Approved On: 8/7/2018 
 
 
Consent and Authorization 
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 
study. 
 
 
TO BE FILLED OUT BY SUBJECT ONLY 
Please print your name, sign, and date below if you agree to be in the main study. By signing this 
consent and authorization form, you will not give up any of your legal rights. We will give you a copy of 
the signed form to keep. 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Subject 
 
 
 
 
 
 
 
 
 
 
 
 
____:____ am / pm 
Signature of Subject 
 
 
 
       Date 
 
    Time    (please circle) 
 
 
TO BE FILLED OUT BY STUDY TEAM ONLY 
 
 
 
 
 
 
 
 
 
 
Printed Name of Person Obtaining Consent 
 
 
 
 
 
 
 
 
 
 
 
 
____:____ am / pm 
Signature of Person Obtaining Consent  
       Date 
 
    Time     (please circle) 
 
 
 
PI: Omer Kucuk, MD and Viraj Master, MD PhD                   Page 8 of 11                                       Version Date: 08/02/2018 
    EU2010-11 (Gibbs)                                                                                                                             IRB Form 09052017