Clinical trial NCT02441062
Conditions: Neuroendocrine Tumors Carcinoid Tumors Neuroblastoma Medulloblastoma
Sponsor: Sue O'Dorisio
Start date: 2015-09-01; Completion date: 2020-01-20
Enrollment: 122 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Participants in this study have been diagnosed with a tumor such as a carcinoid, neuroendocrine tumor, neuroblastoma, Ewing's sarcoma, or brain tumor that has cells which carry somatostatin receptors.

The purpose of this research study is to see if the tumor can be identified using a special procedure called a positron emission tomography (PET) scan and how the results of this imaging procedure will change the management of the tumor.

Detailed description:
This is a prospective, Phase II, single center, open-label study in a total of 200 participants with histologically proven neuroendocrine tumor or other somatostatin receptor positive tumors. Eligible participants will undergo baseline assessments at enrollment. They will receive 68Ga-DOTATOC and undergo a PET/CT imaging study. Participants may receive a second 68Ga-DOTATOC PET/CT for restaging after therapy 12-36 months following the first scan.

Arms: arm 1: Study participants will receive 68Ga-DOTATOC and undergo a PET/CT imaging study. Subjects may receive a second 68Ga-DOTATOC PET/CT for restaging after therapy 12-36 months following the first scan.
Interventions: intervention 1: 68Ga-DOTATOC PET/CT
Intervention descriptions: intervention 1: Ga-68 DOTATOC PET-CT on management of patients with somatostatin receptor positive tumors

Protocol documents:
Prot_SAP_001.pdf: 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
1 
 
 
 
 
 
Impact of Ga-68 DOTATOC PET/CT on Management of 
Somatostatin Receptor Positive Tumors 
 
Principal Investigator: M. Sue O’Dorisio, MD, PhD 
Co-Principal Investigator: Yusuf Menda, MD 
 
Co-Investigators: 
Thomas O’Dorisio, MD 
Joseph Dillon, MD 
Gideon Zamba, PhD 
Michael Graham, PhD, MD 
Parren McNeely, MD  
David Bushnell, MD  
David Dick, PhD 
Janet Pollard, MD 
Michael Schultz, PhD, 
Laura Ponto, PhD 
John Sunderland, PhD 
Blanca Schafer, MS, CCRP 
Shannon Lehman, BA 
 
 
 
 
 
 
Mary Schall, RN, BSN 
 
Document type: PROTOCOL FOR IND# 114,398 
Version number: 4 
IRB# 201503708 
Date: February 22nd, 2016 
 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
2 
 
 
 
 
TABLE OF CONTENTS 
I. Introduction…………………………………………………………..…3 
II. Rationale and overall study design ………………………………..…4 
III. Clinical Protocol………………………………………………….….….5 
IV. Chemistry, Manufacturing and Control………………………...….. 13 
V. Labeling…………………………………………………………...….. 15 
VI. Pharmacology and Toxicology……………………………………… 15 
VII. Previous Human Experience …………………………………........15 
VIII. Justification of Request to Charge………………………………...18 
IX. References………………………………………………………….…20 
 
 
Appendices: 
I. Data Safety Monitoring Plan 
II. Sample Case Report Forms 
III. Menda Y, Ponto LB, Schultz MK, Sunderland J, O’Dorisio TM, O’Dorisio MS. 
Repeatability of Ga-68 DOTATOC PET Imaging in Neuroendocrine Tumors. Pancreas. 
2013 42: 937-43. PMCID: PMC3898770 
 
 
 
 
Project Goal 
Evaluate the impact of Ga-68 DOTATOC PET-CT on management of patients with 
somatostatin receptor positive tumors 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
3 
 
 
 
 
 
I. Introduction: 
 
Neuroendocrine Tumors 
Neuroendocrine tumors are solid malignant tumors that arise from dispersed neuroendocrine cells found 
throughout the body. Gastroenteropancreatic neuroendocrine tumors (NETs) can be divided into two 
groups: Carcinoid tumors that may arise from the lungs, stomach, small bowel or colon and pancreatic 
neuroendocrine tumor. The clinical behavior of NETs is extremely variable; some may cause hormone 
hypersecretion and others may not, the majority of them are slow-growing tumors (well-differentiated 
NETs), whereas some NETs are highly aggressive (poorly differentiated NETs). The incidence of NETs is 
increasing, from 1.1/100,000 per year in 1973 to 5.3/100,000 per year in 20041. Among NETs, 25% have 
distant metastases and 25% have regional involvement at the time of initial diagnosis1. 
Surgery is the only curative option for NETs; however, curative surgery in malignant NET is possible in 
less than 30% of patients. Treatment with somatostatin analogs, which include the short acting 
subcutaneous and long acting release (LAR) octreotide, are effective in stabilizing NETs and have been 
recently demonstrated to prolong the time to progression of disease2. Chemotherapy is generally not 
effective in low grade NETs, but it may be helpful in high grade and pancreatic NETs. Other specific 
therapies in NETs are the mTOR-inhibitor everolimus, which in combination with octreotide has been 
shown to improve progression free survival by approximately 6 months in pancreatic NETs3. The tyrosine 
kinase inhibitor sunitinib has also demonstrated significant antitumor efficacy in pancreatic NETs4. 
 
Conventional Imaging of Neuroendocrine Tumors 
The radiological detection and staging of neuroendocrine tumors is challenging and requires a 
multimodality approach. CT is usually the initial imaging modality in staging and restaging of 
neuroendocrine tumors. The performance of CT in detection of NET is variable depending on the location; 
the sensitivity also drops significantly in lesions smaller than 1cm5. MRI may be more sensitive than CT 
for liver and bone marrow metastases, but small nodal metastases may be missed on both imaging 
modalities6. 
 
The standard nuclear medicine technique for imaging NET is somatostatin receptor scintigraphy with In- 
111 Octreotide (OctreoScan®), which primarily targets the somatostatin receptor subtype 2 (sstr2) on 
NET (Figure 1). The sensitivity of In-111 Octreotide is >90% for well-differentiated carcinoid tumors and 
majority of pancreatic NETs, but is lower for NETs with weaker expression of sstr2 such as insulinoma 7. 
The sensitivity of OctreoScan is lower for small tumors less than 1 cm due to the resolution limits of 
SPECT (Single Photon Emission Computerized Tomography) imaging and may be also limited in 
detection of liver metastases due to high background hepatic uptake8. 
 
Somatostatin Receptor PET Imaging with 68Ga-DOTA0-Tyr3-octreotide 
More recently, positron emission tomography (PET) radiopharmaceuticals have been developed that can 
be labeled with Gallium-68 (Ga-68). Gallium-68 is a generator product with a half-life of 68 min (compared 
to 67 hours for In-111 in OctreoScan). The parent nuclide of Ga-68 is Germanium-68, which has a half- 
life of 270.8 days. Ga-68 decays by 89% through positron emission and 11% by electron capture. A 
number of Ga-68 DOTA-conjugated peptides have been introduced, including 
68Ga-DOTA0-Tyr3- 
octreotide (68Ga-DOTATOC), 
68Ga-DOTA0-1NaI3-octreotide (68Ga-DOTANOC) and 
68Ga-DOTA0-Tyr3- 
octreotate (68Ga-DOTATATE)  (Figure 2). All of these radiolabeled peptides bind to sstr2, although 
DOTANOC also binds to sstr3 and sstr5, and DOTATOC to sstr59. The advantages of Ga-68 based 
somatostatin receptor PET imaging over OctreoScan SPECT involve the higher imaging resolution, the 
higher affinity of the radiopeptide for the sstr2 and the accurate quantitation of uptake due to robust 
attenuation correction. 68Ga- DOTATOC has been found to be superior to OctreoScan in detection of 
skeletal and pulmonary involvement of neuroendocrine tumors10. 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
II. Rationale and overall study design 
Rationale: 
68Ga-DOTATOC positron emission tomography (PET) is not approved for use in the United States.  IND 
#114,398 is currently active under the above named investigators for imaging with Ga-68 DOTATOC PET 
and IND #61,907 is active for treatment with 90Y-DOTATOC PRRT in somatostatin receptor positive 
tumors. We have conducted a single institution Phase II trial of safety and efficacy of 68Ga-DOTATOC 
PET in neuroendocrine tumors (see “Previous use in Humans”). 
 
The purpose of this protocol is to evaluate the impact of 
68Ga-DOTATOC PET/CT imaging on 
management of patients with somatostatin receptor positive tumors. 68Ga-DOTATOC PET/CT would 
replace 111In-DTPA-Octreotide single photon emission tomography (SPECT/CT) imaging in view of its 
significant advantages: (1) 68Ga-DOTATOC has a higher affinity for somatostatin receptors (sstr2) 
compared to Octreoscan 11; (2) The radiation dose from 68Ga-DOTATOC is significantly lower compared 
to In-111 Octreotide, 3.4 mSv versus 12 mSv for standard administered doses12; (3) [68Ga]DOTATOC 
PET/CT can be completed within 2 hours compared to an Octreoscan which requires 3 visits over 24 
hours, making 68Ga-DOTATOC a much more convenient imaging choice for patients. 
 
Overall Study Goal and Study Design 
Project Goal 
This study is planned to evaluate the impact of 68Ga-DOTATOC PET/CT imaging on management of 
patients with somatostatin receptor positive tumors. 
 
Project Design 
This is a prospective, Phase II, single center, open-label study in a total of 200 subjects with histologically 
proven neuroendocrine tumor or other somatostatin receptor positive tumors. Eligible participants will 
undergo baseline assessments at enrollment. Study participants will receive 68Ga-DOTATOC and 
undergo a PET/CT imaging study. Subjects may receive a second 68Ga-DOTATOC PET/CT for 
suspected disease progression, for restaging prior to institution of new therapy, or for measurement of 
disease response after therapy. This second scan may be obtained at any time from 6-36 months following 
the first scan. 
Figure 1 Chemical identity of [68Ga]DOTATOC 
IND # 114,398 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
5 
 
 
 
Participant Enrollment 
Participants will be recruited from the Neuroendocrine Tumor Clinics at the University of Iowa 
Comprehensive Cancer Center Clinics and the University of Iowa Children’s Hospital. Participants may 
also request to join the study via clinicaltrials.gov. 
 
 
 
 
 
 
 
Schema 
 
 
 
 
 
Figure 2 Study Schema 
 
III. Clinical Protocol 
Inclusion Criteria: 
 
1. Age ≥ 6 months. 
2. Histologically  diagnosed or suspected (pediatric only) neuroendocrine  tumor  or  other  tumor  
with  probable  somatostatin receptors subtype 2 
3. Karnofsky performance status or Lansky Play Scale status of ≥  60 (or ECOG/WHO equivalent). 
4. Subject  is  male;  or  is  a  female  who  is  either surgically  sterile  (has  had  a documented  
bilateral  oophorectomy  and/or  documented  hysterectomy),  postmenopausal  (>1 years without 
menses), ≥60 years old,, or of childbearing potential for whom a pregnancy test (with the results 
known prior to investigational product administration) is negative. A negative pregnancy test will be 
required for all female subjects with child bearing potential. If a false pregnancy test is suspected, 
e.g., perimenopausal condition, an obstetrician will be consulted to determine if she is/is not 
capable of becoming pregnant. Female must also be non-lactating. 
 
Exclusion Criteria 
 
5. Subject weighs more than 450 pounds (Subjects who weigh more than 450 pounds will not be 
able to fit inside the imaging machines) or otherwise cannot be safely fit into the imaging system. 
6. Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.) 
7.  Inability to complete the needed investigational and standard-of-care imaging examinations due to 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
other reasons (severe claustrophobia, radiation phobia, etc.) 
8.  Any additional medical condition, serious intercurrent illness, or other extenuating circumstance 
that, in the opinion of the investigator, may significantly interfere with study compliance. 
9. Peptide receptor radionuclide therapy (PRRT) within 4 weeks of Ga-68 DOTATOC PET/CT scan 
10.  Treatment with Sandostatin LAR within 4 weeks, SQ Octreotide within 12 hours, or Lanreotide 
injection within 8 weeks of Ga-68 DOTATOC PET/CT (+/-5%) 
Procedures Informed 
Consent 
Subjects w h o  a p p e a r  t o  meet eligibility criteria will be consented. After consent, subjects are 
considered actively enrolled in the study and a study log will be maintained. Record of consent will be 
scanned into the patient’s electronic chart and the original consent will be placed in the patient’s research 
folder. 
 
Physical Examination and Medical History 
Physical examination a n d  m e d i c a l  h i s t o r y  will be performed to ensure suitability according to 
the inclusion and exclusion criteria at screening ( V i s i t  1 )  a n d  a d v e r s e  e v e n t s  w i l l  b e  
c o l l e c t e d  at the time points specified in the Schedule of Events (Table 1). 
 
Table 1. Schedule of Study Events 
 
Visit 1a 
Scan  
(Visit 2) 
1 Day 
(18-36hrs)c 
1-14 
Days 
6-18 
monthsg 
Informed consent 
X 
 
 
 
 
Medical history 
X 
 
 
 
 
Physical examination 
X 
 
 
 
X 
Concomitant meds 
X 
 
 
 
X 
Blood pressure, temp, 
respiratory rate, heart 
rate, weightd, heightd 
X 
X 
 
 
X 
Pregnancy test (serum) 
Xb 
Xf 
 
 
Xf 
68Ga-DOTATOC 
PET/CT 
 
X 
 
 
X 
Pre-scan forme 
X 
 
 
 
X 
Post-scan forme 
 
 
 
X 
X 
Adverse events 
 
X 
X 
 
X 
a- (-60 to 0 days) To facilitate scheduling, some screening procedures may occur up to 2 months 
prior to the first dose of study drug. 
b- A serum pregnancy test  
c- phone call  
d- Height and weight at Visit 1. Values will be obtained from EPIC notes. 
e- see form in Appendix II 
f- A urine pregnancy test may be obtained if serum pregnancy test was obtained more than 24 
hours prior to scan 
g- A second PET scan will be offered to patients who undergo surgery/PRRT/targeted 
therapy/chemotherapy. This will comprise  Visits 3, 4 and an additional phonecall. The requirements 
will be the same as visits 1, 2 and the follow up phonecall. 
 
 
 
Events in Table 1 will be repeated (except for informed consent unless a new version is available) if patient 
is eligible for the optional second scan. Patients undergoing surgery, PRRT, targeted therapy or 
chemotherapy in response to the results of the first PET scan will be eligible for a second, follow up PET 
scan per their physician’s recommendation. The medical history will elicit information concerning existing 
medical conditions, major illnesses, and related surgical procedures. Any prescribed or over-the- counter 
medications that the subject received within the past 30 days should be recorded on the case report form. 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
 
Pregnancy Test 
Female subjects of childbearing potential will have a pregnancy test (serum or urine) before exposure to 
research-related radiation. 
A woman who is pregnant may not participate in this study and must tell us if 
she may have become pregnant during the previous 14 days because the pregnancy test is unreliable 
during this time. If a false positive pregnancy test is suspected, e.g., perimenopausal condition, an 
obstetrician will be consulted to determine if she is/is capable of becoming pregnant. 
 
68Ga-DOTATOC PET/CT Scan 
Study participants who complete Visit 1 and have been deemed eligible, will undergo the  68Ga-DOTATOC  
PET/CT.  Subjects may be offered a medication (alprazolam or lorazepam) to help them relax. The 
injected dose for adults will be 3-4 mCi (target: 4 mCi +/- 10%) containing <50 μg 68Ga-DOTATOC and will 
be injected via IV access lines (peripheral or central lines are acceptable.).  The dose for children will be 
0.043 mCi/kg with a maximum dose of 3 mCi.  A low tube current CT will be obtained for attenuation 
correction and localization of PET/CT data. If a diagnostic CT scan is also clinically indicated, this can be 
performed on the PET/CT system in the same imaging session. All investigational PET/CT scans will be 
read by a board-certified nuclear medicine physician with established expertise. A report will be generated 
for the site(s) of the primary tumor (if visible/present) and metastases, which will be entered into the 
patient’s medical record. If contrast-enhanced CT scans are obtained, these will be interpreted by the 
subspecialty radiologist per clinical routine and entered into the chart. 
 
Investigational Radiopharmaceutical Administration 
68Ga-DOTATOC will be administered intravenously in conjunction with the PET/CT scan. The one-time 
nominal injected dose will be 4mCi (+/- 10%) containing <50 μg 68Ga-DOTATOC (estimated, allowing 
for adherence of peptide to glassware or syringes, a portion of the 50 μg original quantity used 
for QC, etc). The pediatric dose will be 0.043 mCi/kg with a minimum dose of 0.3 mCi and a maximum 
dose of 3 mCi in children <18 years old. 
 
68Ga-DOTATOC is produced at the University of Iowa PET Imaging Center by qualified personnel following 
USP <823> standards. All quality control tests will be completed satisfactorily prior to final release of 
the drug product, with the exception of sterility testing (test takes two weeks for completion). Subjects will 
be observed and monitored in the PET/CT area until the scan is completed which  is approximately 
for 90 min after the administration of 68Ga-DOTATOC (60 min uptake period before imaging starts and 
approximately 30 min imaging time). The subject or his/her guardian will be queried for constitutional 
symptoms suggesting an adverse reaction to the investigational radiopharmaceutical.  These will be 
evaluated as a drug-related adverse reaction.  Staff will release subjects from clinic as appropriate, based on 
query results. The following day, all subjects will be contacted by phone or seen in the clinic and again asked 
if untoward/adverse events occurred after release. Any observed adverse events will, of course, be treated 
immediately and appropriately, and reported to the University of Iowa IRB and the FDA in accordance 
with established guidelines. 
 
Data Analysis: 
The primary end-point of the study is the change in management of patients based on findings of the 
68Ga-DOTATOC PET/CT scan. UIHC referring physicians will be asked to fill out pre-PET and post-PET 
scan forms (Appendix II) to provide information on the management and treatment strategy of the 
patient before the 68Ga-DOTATOC PET/CT and after the information from the 6 8Ga-DOTATOC 
PET/CT study is available. This is the same methodology used in the National Oncologic PET Registry 
study; change in management strategy criteria are modified for the specific treatment strategies used in NET 
(Table 2). 
 
Table 2: Criteria for minor change, major change and no change in management strategies based on 
comparison of pre-PET and post-PET plans. 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
 
 
Subjects whose post-scan treatment plan represents a major change (whether or not the pre-scan treatment 
plan was a major change), will be presented at the Neuroendocrine Tumor Board, for a consensus 
recommendation regarding treatment.  The minutes of this tumor board discussion and recommendation will 
be retained with the subject’s study chart. 
 
Risks 
 
Risks of Study Drug 
Research radiation dose estimate: Our calculations estimate that the effective whole-body dose of the 
68Ga-DOTATOC PET/CT is approximately 1.6 rem, less than the radiation dose from a conventional 18F- 
FDG PET/CT scan of about 2.4 rem, assuming the standard use of a “low-dose” CT for anatomic 
localization and attenuation correction, as described in our proposed imaging protocol. The U.S. national 
annual background dose for humans is approximately 0.36 rem. The maximum annual permissible whole 
body radiation dose to a career radiation worker (e.g., a radiologist, nuclear medicine technologist, etc.) is 
5.0 rem. Thus, the one-time dose to the patient for the investigational PET/CT will be approximately one- 
third of the annual permissible dose to a career radiation worker and about 5 years’ worth of background 
radiation in the US. The increased risk to the patient, who will have a known current life-threatening 
malignancy, for a second radiation-induced malignancy from this investigational radiation exposure is 
extremely low (estimated < 1%).  Given the risk of death from either delay in diagnosis or under-treatment 
of these known malignancies, we feel the added radiation burden to the patient is well within the patient’s 
best interest if 68Ga-DOTATOC PET/CT imaging adds value. 
 
Risks of Study Procedures 
Risks of Investigational PET/CT:  An  adverse  reaction  to  the  investigational radiopharmaceutical is 
possible though not reported. Additional risks include radiation exposure from the investigational PET/CT 
8 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
9 
 
 
 
scan, dosage infiltration, risks from IV access, and the inconvenience of the investigational PET/CT scan. 
If a subject elects to take medication to help them relax for the scan, they may experience drowsiness or 
unclear thinking. They will be instructed not to drive or operate machinery for 12-24 hours after receiving 
the medication. A driver will be required, if this type of medication is given the day of the scan. 
 
Children may require sedation or anesthesia to remain still during the PET scanning procedure. The risks 
of sedation include a reaction to the medication used for sedation or anesthesia. If anesthesia is 
required, there is a risk of injury to the throat or airways from insertion of the breathing tube. 
Reporting Adverse Events or Unanticipated Problems involving Risk to Subjects or Others 
Adverse Event Terminology 
Adverse Event 
1. An AE is “any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this treatment”. 
An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not considered related to the medicinal (investigational) product. AEs 
include any of the following: 
• 
Subject deterioration due to the primary illness at the onset of the trial 
• 
Intercurrent illnesses 
• 
Drug interactions 
• 
Events related or possibly related to concomitant medications 
• 
Abnormal laboratory values or changes of vital signs, as well as significant shifts from baseline 
within the range of normal, considered to be clinically significant by the Investigator. 
 
2. Adverse Drug Reaction 
In the pre-approval clinical experience with a new medicinal product or its new usage, particularly as the 
therapeutic dose(s) may not be established, an adverse drug reaction is defined as: 
All noxious and unintended responses to a medicinal product related to any dose should be considered 
adverse drug reactions (ADR). 
3. Unexpected Adverse Drug Reaction 
An unexpected ADR is: 
• 
An adverse drug reaction, the nature or severity of which is not consistent with the applicable 
product information, also known as reference safety information. 
 
4. Serious Adverse Event/Serious Adverse Drug Experience 
During clinical investigations, serious AEs may occur. If the event is suspected to be drug-related, the 
event may be significant enough to lead to important changes in the way the medicinal product is 
developed (e.g. change in dose, population, needed monitoring, consent forms). This is particularly true 
for reactions, which, in their most severe forms, threaten life or function. A serious AE (SAE) or serious 
adverse drug experience (SADE) is any untoward medical occurrence that: 
• 
Results in death. 
• 
Is life-threatening. ‘Life-threatening” refers to an event in which the subject is 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 (ICHE6). 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
• 
Results in persistent or significant disability/ incapacity (as per reporter’s opinion). 
• 
Is a congenital anomaly/birth defect. 
• 
Is another medically important condition. Important medical conditions that may not result in death, 
be life-threatening or require hospitalization may be considered as SAEs or SADEs when, based 
upon appropriate medical judgment, they may jeopardize the subject or may require intervention 
to prevent one of the outcomes listed in the definition above. Examples of such events are 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
10 
 
 
 
intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias 
or convulsions that do not result in hospitalization; or development of drug dependency or drug 
abuse. 
• 
[Code of Federal Regulations Title 21, Volume 5, 21CFR312.32, revised April 1, 2006]. 
• 
Please note: Serious is not synonymous with severe. An event may be severe (e.g., severe 
headache) but still be of minor medical significance. Serious refers to an event that poses a threat 
to the subject’s life or functioning. 
 
5. Assigning Severity to an Adverse Event 
Severity of adverse events will be graded according to NCI Common Terminology Criteria for Adverse 
Events version 4.0 (CTCAE v4.0) which is available at http://ctep.cancer.gov/reporting//ctc.html. 
 
6. Assigning Relationship of Adverse Event to Study Drug (Causality) 
The Investigator will determine the relationship of each adverse event. Descriptions of the three  
classification categories are as follows: 
Not Related 
Exposure to study drug has not occurred; administration of study drug and the adverse event are not 
reasonably related in time; or the AE is considered by the Investigator to be due to a pre-existing 
condition, a known manifestation of the target disease, a recurrent condition, or is likely explained by 
environmental or diagnostic therapeutic factors or was preexisting and did not deteriorate. 
Possibly Related 
The AE occurred during or within a reasonable period of time after administration of the study drug, or a 
pre-existing event worsened within an appropriate period of time after administration of study drug, but 
the AE could be explained equally well by factors or causes other than exposure to the study drug. This 
category will also be used if there is a lack of information, or insufficient or conflicting evidence exists for 
classifying the causality of the AE. 
Probably Related 
The AE occurred during or within a reasonable period of time after administration of the study drug or a 
pre-existing event worsened within an appropriate period of time after administration of study drug, and at 
least one of the following criteria is applicable: 
• 
the event could not be explained by the clinical condition or history of the subject, environmental 
or toxic factors, or other diagnostic or therapeutic measures; 
• 
the event was an expected ADR associated with study treatment or a class-labeled drug effect; 
• 
the AE subsided or disappeared after withdrawal or dose reduction of study treatment; or 
• 
the AE recurred after re-exposure to study treatment. 
 
Adverse Event Recording and Reporting 
1. Adverse Event Recording 
At baseline, all SAEs and study-related AEs since signing of the Informed Consent Form will be recorded. 
After initial study drug administration, all AEs will be recorded. Each AE occurring to a subject, either 
spontaneously revealed  by the subject or observed by the Investigator, whether believed by the 
Investigator to be related or unrelated to the study drug, must be recorded on the AE Case Report Form 
and on the subject’s file. Subjects will report the type and severity of AEs without being given a list of 
fixed symptoms beforehand. The Investigator will determine the relationship of any AE to study drug 
(causality) and record it on the appropriate section of the AE CRF as well as the start date of the event, 
event  grade, and whether or not the event meets one or more of the definitions of an SAE.  Clinically 
significant changes in vital signs (e.g., tachycardia) or other clinically significant changes observed by 
the physician will be entered in the appropriate CRF.  


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
11 
 
 
2. Serious Adverse Event Reporting 
All SAEs  must  be  reported  promptly  to  the  PI  and  will  follow  IRB  and  IND  regulatory  reporting 
requirements. SAEs should be followed to resolution or stabilization, even if this is after the study reporting 
period. 
 
Data and Safety Monitoring 
See Appendix 1 for Data and Safety Monitoring Plan 
 
Assessing Toxicity: 
Toxicity will be graded according to NCI’s Common Toxicity Criteria (CTCAE v4). The principal 
investigator will responsible for determining the attribution of toxicity as it is related to the investigational 
drug. All grades of toxicity will be noted and reported appropriately. 
Adverse Event Reporting: 
The clinical research coordinator is responsible for collecting and recording all clinical data. As these 
results are collected, all toxicities and adverse events will be identified and reported to the principal 
investigator. The principal investigator will determine relationship of the event to the study drug and 
decide course of action for the study participant. As part of the ongoing monitoring of this study, the PI will 
maintain an AE summary table to be reviewed during the quarterly audits. 
 
For Guidelines of Routine Adverse Event Reporting See Appendix 1 
Study Withdrawal/Discontinuation 
This is a low risk imaging protocol; the amount of radioactive peptide is below physiological effects level 
and the radiation dose is below allowable levels. No adverse events are expected. Adverse events are 
recorded on the CRF at the following times: 
- at the conclusion of the PET/CT scan (approximately 90 min after the injection of the 
radiopharmaceutical) 
- during phone call 18-36 hrs after PET/CT 
At any time, subjects may withdraw from the study (i.e., withdraw consent to participate) at their own 
request. A subject’s participation in the study may be discontinued at any time at the discretion of the 
Investigator and in accordance with his/her clinical judgment. No disadvantage will arise for any subject 
who withdraws consent for participation at any time or who is withdrawn from the study by the 
Investigator. Reasons for discontinuation of study treatment will be recorded on the appropriate page of 
the CRF in any case and may include the following: 
 
• 
Subject's request for withdrawal 
• 
Investigator's decision that discontinuation is in the best interest of the subject 
• 
Non-compliance with the regimen and timing that might result in dropping out from the study 
• 
Development of an intolerable AE due to study participation as determined by the Investigator, 
subject, or both. 
• 
Development of an intercurrent illness, condition, or procedural complication, which would interfere 
with the subject's continued participation. 
• 
 
 
Statistical Considerations 
 
This study will evaluate the impact of 
68Ga-DOTATOC PET/CT imaging in the management of 
patients with neuroendocrine tumors and other somatostatin receptor positive tumors. Participants will be 
recruited from the Neuroendocrine Tumor Clinics at the University of Iowa Comprehensive Cancer Center 
Clinics and the University of Iowa Children’s Hospital, and individuals may also request to join the study 
via 
clinicaltrials.gov. The 
study 
will 
be 
open-label and 
subjects 
with 
histologically proven 
neuroendocrine tumor or other somatostatin receptor positive tumors will be recruited. Subjects will 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
12 
 
receive 68Ga-DOTATOC and undergo a PET/CT imaging study. The endpoint of the study will be the 
change in management of patients based on findings of the 68Ga-DOTATOC PET/CT scan. Three levels 
of change will be assessed: no change, minor change and major change based on findings after 
receiving 68Ga-DOTATOC and undergoing PET/CT. A previous pilot study of 70 patients (46 of which 
meet our current inclusion criteria), suggested that 37% of the population had experienced a major 
change in patient management following 68Ga-DOTATOC imaging. We operate under the assumption 
that a  49% major change in management within this population will be clinically relevant should 68Ga-
DOTATOC induce clearer image prompting change. 
 
A sample size of 180 patients achieves 90% power to detect a difference of 12% using a two-sided Z test 
(also a binomial exact test reaches similar power) when the null hypothesized proportion was used to 
estimate the standard deviation. The target significance is 0.05 and the actual significance level is 0.045. 
The results on power justification assume that the proportion of major change in patient management is 
37% under the null. Note that we design the power around a two-sided alternative so we can gain more 
power for the one-sided (as our medical intuition seems to suggest.) 
 
There is a potential for loss to follow-up or attrition within this population. We estimate this rate to be 
around 10%. In order to have 180 evaluable patients, our estimated sample size is 180 / (.90) = 200 
subjects. 
 
We will test the null hypothesis of 37% versus a clinically relevant alternative of 49% of major change in 
patient management. If the null is rejected at significance level of 0.05, we will have enough evidence to 
attribute our decision to 68Ga-DOTATOC effect. 
 
Within each category of patient management change (No—Minor—Major), we will report the estimated 
proportion of subjects as well as 95% confidence intervals around these estimates. 
 
Privacy/Confidentiality Issues 
All routine medical data will be entered into the patient’s electronic medical record. These records are 
only available to those with direct clinical duties to the patient. For all other records, the Principal 
investigator will collect data and store this source data in a locked office. Each patient will have a unique 
identifier number( e.g. IMPACT001, IMPACT002) . A log of patient study ID’s and Medical Record 
Numbers will be stored in our secured OnCore database. Only research associates or those individuals 
directly involved with the study will have access to data. Information is for research purposes only and 
when used for publication purposes, all participants will have their names concealed. Access to identified 
patient information will be limited to the investigators listed within the IRB application. De-identified 
information with HIPAA identifiers removed will be available to other investigators following IRB approval. 
Confidentiality and security will be maintained for the database. 
 
The database is stored behind a firewall (in addition to the institutional firewall) with the highest level of 
protection, i.e. the same level of protection as the on-line hospital information systems at the University of 
Iowa Hospitals. This means that users must logon to a web server that sits between the institutional firewall 
and the firewall to the database, and only this application server is allowed to query the database. Only 
users approved through our institutional review boards will be allowed access to patient identifiers. Other 
levels of authorization may exist for future approved users following IRB approval, e.g. access to de-
identified data. 
 
Data is initially collected in the medical record or research record for each individual study participant. The 
information will be extracted from the patient’s medical record and research record and then transferred 
into the Case Report Form (CRF). The study data will be kept on site and in a securely locked room to 
protect patient confidentiality. The CRFs do not include personal identifiers for any participant.  Study 
personnel (PI and co- investigators) and government regulatory agencies have access to all research 
records as required by law. Others (such as law enforcement agencies) may have access to records as 
defined by law. 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
13 
 
 
Record Retention 
The PI must retain all study records by the applicable regulations in a secure and safe facility. The 
institution must consult with the PI before disposal of any study records, and must notify the PI of any 
change in the location, disposition or custody of the study files. The PI/institution must take measures to 
prevent accidental or premature destruction of essential documents, that is, documents that individually 
and collectively permit evaluation of the conduct of a study and the quality of the data produced, including 
paper copies of study records (e.g., subject charts) as well as any original source documents that are 
electronic as required by applicable regulatory requirements. Records and documents pertaining to the 
conduct of this study, including Case Report Forms (Appendix III), source documents, consent forms, 
laboratory test results, and medication inventory records, must be retained by the investigator for at least 2 
years following submission of a New Drug Application. No study records will be destroyed without prior 
authorization from the Principal Investigator. 
 
IV. Chemistry, Manufacturing, and Control 
The University of Iowa PET Center Radiopharmaceutical Laboratory maintains an environment that is 
adherent to USP <823>. Reagents used for the preparation of [68Ga]-DOTATOC are received and 
inspected per specification sheets and accepted or rejected. Accepted reagents are labeled with 
appropriate expiration dates, initialed, assigned identification numbers, and quarantined in specified 
locations in the radiopharmaceutical laboratory. 
 
The University of Iowa (UI) PET Center Radiopharmaceutical Laboratory is staffed with expert 
radiochemists that oversee the preparation of the radiopharmaceuticals and are experienced in the 
compounding of the proposed investigational radiopharmaceutical, having prepared over 200 patient doses 
of 68Ga-DOTATOC for phase I IND studies. 
Because Ga-68 has a 68 minute half life, production of 68Ga-DOTATOC requires the use of a Germanium- 
68 (Ge-68) to Ga-68 generator. The eluted Ga-68 is purified following elution using an ion-exchange column 
prior to introduction into the radiolabeling vessel with DOTATOC to remove zinc-68 (the decay product of 
Ga-68), which builds up in the generator with the decay of Ga-68. 
 
According to the 68Ga-DOTATOC Batch Record, the generator is connected to the ModularLab 
PharmTracer module and eluted with 0.1 N HCl directly to an ion exchange column for purification of the 
Ga-68 from Zn-68 (daughter nuclide of Ga-68 decay). The system includes a disposable GMP-certified 
(sterile, pyrogen-free) cassette that is snapped in place and manages (via software) the flow of reagents 
for purification, radiolabeling, and transfer of the final product to the product vial via sterilizing (0.22 μm) 
filter. A new cassette is used for each preparation and preparations are used for one or two patient 
studies. At the end of the process, the generator line is disconnected, capped, and the generator stands 
ready for connection to a new kit for a new preparation. 
 
The system then elutes Ga-68 with acetone/0.02 N HCl solution directly to a reaction vessel containing 50 
micrograms of DOTATOC (obtained commercially) dissolved in 2 mL of sodium acetate buffer (pH 4). The 
solution is heated to 95°C for 7 minutes at which time the heating element is turned off and the vessel is 
cooled with the addition of 2 mL isotonic saline for injection. Acetone is removed by distillation during the 
radiolabeling process and a test for residual acetone is included in subsequent quality control prior to 
release. 
 
The solution is next passed over a disposable tC18 cartridge, which retains 68Ga-DOTATOC while 
allowing any remaining free Ga-68 to pass through. The cartridge is rinsed with isotonic saline for 
injection to remove any residual free Ga-68, followed by elution of 68Ga-DOTATOC with 1 mL of 47.5% 
ethanol in water directly through a sterile 0.22 micron filter and into the final collection vial. 
 
A 0.8 mL aliquot is taken for quality control testing. Radiochemical yields of approximately 55% 
(uncorrected for decay) are routinely achieved using this process. The final sterilizing filter is retained for 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
14 
 
a QC pressure test to ensure filter integrity for sterilization. The production process can be conducted by 
a single person and requires approximately 1 hr to complete. Quality control procedures are usually 
carried out by two people to expedite delivery. The QC process takes approximately 20 minutes. 
 
The quality control tests are performed and compared to release criteria prior to release of the final 
product as shown in Table 3. 
 
Table 3. Analytical Specifications 
Test 
Release Criteria 
Appearance 
Clear and no visible impurities 
Sterile Filter Test 
2 bar for 1 minute 
pH 
4.0 – 7.0 
Radiochemical purity 
>90% 
Endotoxins 
<17.5 EU per mL 
Acetone 
<5000 ppm 
Ethanol 
<10% 
Radionuclidic 
Half life +/- 30 seconds 
 
Filter Test: A filter pressure test is conducted by applying pressure to the sterilizing filter at 2 bar inert gas 
(nitrogen or argon) for 1 minute to ensure the integrity of the filter for sterilization. 
 
Bacterial Endotoxins: Bacterial endotoxin test following a 50:1 dilution. Endotoxin/Limulus Amebocyte 
Lysate (LAL) testing using Endosafe-PTS Cartridges or alternative gel-clot vials as backup. 
 
pH: The pH of the final product should fall within the limits of 4.0-7.0 and is measured by spotting pH 
paper. 
 
Radiochemical Purity: The system utilizes iTLC-SG media and 0.2 M Citric acid: ethanol (90:10) as the 
solvent. When using this TLC system,68Ga-DOTATOC and free Ga-68 can be differentiated at Rf – 0.0 and 
1.0, respectively. 
 
Sterility: Following release, Tryptic Soy Broth (TSB) and Fluid Thioglycollate Media (FTM) are inoculated, 
incubated (TSB at 22.5 °C, FTM at 32.5 °C) and checked for growth during the ensuing 14 days. 
 
Acetone: When acetone is used in the purification process, a gas chromatography test is used for 
analytical specification. 
 
Ethanol: When ethanol is used in the purification process, a gas chromatography test is used for analytical 
specification. 
 
Radionuclidic Purity: Half life measurement is determined by continuous measurement of radioactivity 
signal over 5 minutes and evaluation of the slope of the decay curve. The half life specification is  
obtained from Evaluated Nuclear Structure Data File (ENSDF) at the National Nuclear Data Center 
(NNDC) which can be accessed at www.nndc.gov . Additional standard operating procedures include out of 
specification investigations and reprocessing in the event of a 0.22 micron filter failure. 
 
CMC REFERENCES: 
1. Ocak et al., Full automation of 68Ga labelling of DOTA-peptides including a cation exchange pre- 
purification. (2010). Appl. Rad. Isot., 68;297-302. 
2. Velikyan I., Positron Emitting 68Ga-Based Imaging Agents: Chemistry and Diversity. Med. Chem. 2011 
Jun 28. [Epub ahead of print]. 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
15 
 
3. Capello et al., Cancer Biother. Radiopharm., 18, 761 (2003) 
4. Breeman et al., Eur. J. Nucl. Med. Mol. Imaging, 30, 917 (2003) 
5. de Jong et al., J. Nucl. Med., 46, 13S (2005) 
6. Valkema et al., J. Nucl. Med., 46, 83S (2005) 
7. L.Kolby et al., Br. J. Cancer, 93, 1144 (2005) 
8. Gallium-68 Half Life. Evaluated Nuclear Structure Data File (ENSDF); www.nndc.gov. 
 
V. Labeling 
The final product vial containing 68Ga-DOTATOC will be appropriately labeled. The label will include: the 
name of the radiopharmaceutical, total activity, total volume, radioactive concentration (in mCi/mL), 
specific activity (in MBq/nmol and mCi/µmol), reference date/time and expiration date/time. The label will 
also clearly state that this is a new drug and is limited by Federal (or United States) law to investigational 
use. 
 
The amount of radioactivity injected into the patient’s IV will be recorded immediately prior to injection, with 
residual activity in the syringe recorded immediately after injection. The dose calibrators used in the University 
of Iowa are regularly maintained and calibrated in accordance with current NRC standards. An investigational 
record will be maintained with a copy of each drug label, also documenting time of injection, pre- and post-
injection activity, time and date of injection, and patient identification information. 
Investigational radiopharmaceutical QA/QC information will be maintained for each unit dose for at least six 
years after the closure of this study. These data will provide important information should there be need to 
perform a root cause analysis for a failure-to-perform of a given investigational PET/CT scan. 
 
VI. Pharmacology and Toxicology Information 
The below summary of human experience provides strong evidence that the amount of investigational 
drug (DOTATOC) in mass quantity and the amount of radiation (as also provided via our 
measuredradiation dosimetry) are acceptable in terms of risk. The NOAEL level of DOTATOC has never 
been established in humans, despite some of the below studies reporting much larger mass quantity use 
than we propose, with some using multiple large doses2. The radiation toxicity from the investigational 
radioisotope is also, accordingly, within the acceptable range for patients with life-threatening 
malignancies whose treatment we believe will benefit from the use of the proposed investigational imaging 
procedure. Accordingly, we believe the risk/benefit of our proposed investigation to be justified. 
VII. Previous Human Experience 
Experience at the University of Iowa 
Although there is extensive use of 68Ga-DOTATOC PET/CT in Europe, the limited US experience is 
outlined here. The University of Iowa Radioactive Drug Research Committee and Institutional Review 
Board approved a study entitled “Biodistribution and Reproducibility of Ga-68 DOTATOC Positron 
Emission Tomography in Patients with Somatostatin Receptor Positive Tumors: A Feasibility Study” in 
March 2011. Subjects received two 68Ga-DOTATOC PET/CT scans within 36 hours on each of five 
subjects who were selected based on biopsy proven NET with a positive Octreoscan™ within the past 3 
months. 68Ga-DOTATOC was prepared with GMP grade DOTATOC from Molecular Insight 
Pharmaceuticals using the Eckert-Zeigler ModularLab PharmTracer system. A comparison study is shown 
in Figure 3; the number of lesions is clearly greater with 68Ga-DOTATOC PET compared to Octreoscan; 
biodistribution and reproducibility for these five subjects is summarized in Fig 4 &Table 4. 
 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
16 
 
 
 
Figure 3. 68Ga-DOTATOC PET/CT in a patient with biomarkers and liver mets suggestive of ileal NET, but primary not 
visualized on either high-resolution, contrast CT or Octreoscan. Arrows indicate ileal lesion clearly demonstrated on 
68Ga-DOTATOC PET/CT that was (in retrospect) faintly visible on Octreoscan. Unknown primary lesion in ileum 
confirmed by surgical exploration. Also note addition liver lesions seen on 68Ga-DOTATOC PET/CT. 
 
 
 
 
Table 4. SUV 
reproducibility of [68Ga]-DOTATOC PET lesions 
max 
in patients with metastatic NETs 
Subj ect 1 
Subj ect 2 
Subj ect 3 
Subj ect 4 
Subj ect 5 
Total 
Organs Involved 
Pancreas, bone, 
Lung , bone, 
Hear t, liver, LN 
Bone, liver, 
Lung, bone, LN, 
LN, peritoneum 
LN, liver 
LN 
liver, sm bowel 
% Error * 
5 target lesions 
7.6 ± 7.3 
11.8 ± 9.9 
11.8 ± 7.8 
4.6 ± 4.0 
9.2 ± 5.9 
9.0 ± 7.1 
% Error * 
10 target 
10.4 ± 10.4 
15.7 ± 16.3 
7.4 ± 7.4 
5.0 ± 3.9 
10.7 ± 6.2 
9.8 ± 10.1 
To evaluate the reproducibility of measurement of uptake of 68Ga DOTATOC, 5 patients with metastatic NET 
underwent two DOTATOC PET scans. Standardized uptake values (SUVmax) were measured for 5 target 
lesions (max 2 per organ) and 10 target lesions (max 5 per organ) per subject. Target lesions included 
representative lesions from all involved organs and the lesions with the highest activity for each involved 
organ. Percentage error (i.e. reproducibility) was calculated for each lesion as Percentage Error = 100*ABS 
(Scan 2-Scan 1)/((Scan 2 + Scan 1)/2))13. 
*mean + standard deviation 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 4. Reproducibility of 68Ga-DOTATOC PET in patients with NET. Results for each subject and all 
target lesions in Table 4 are shown. The average (mean ± SD) reproducibility was 10% ±10% for 50 
target lesions. The scatter graph (excluding 2 lesions with SUV>50 for display purposes) shows the high 
correlation of SUVmax of all target lesions on Scan 1 and 2 (R2=0.99). 
 
 
The data analysis of our current safety and efficacy study is ongoing. There were no Grade 2 or higher 
Grade adverse events that were possibly related to Ga-68 DOTATOC in 195 administrations of the 
radiopharmaceutical. A preliminary analysis of the data of 70 patients, 46 of them matching the 
inclusion criteria of the current study, revealed a change in management in 39% of patients. 
 
 
Production of 68Ga- DOTATOC at University of Iowa 
The cGMP grade DOTATOC was purchased from Bachemwith the written permission of Molecular 
Insight Pharmaceuticals, Inc. Radiolabeling was performed using a TiO2 germanium-gallium generator 
and automated ModularLab PharmTracer, both from Eckert-Zeigler Eurotope GmbH. This system utilizes 
a sterile cassette that is replaced for each radiolabeling procedure. Performance has been very 
reproducible with radiochemical, radionuclic, sterility as shown in Table 4. 
 
European Experience in Humans 
The potential of 68Ga-DOTATOC PET/CT for improved imaging of somatostatin receptor positive tumors 
has been recognized since early comparative studies noted improvements in detection sensitivity and 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
18 
 
 
image quality in comparison to [111In]DTPA-octreotide SPECT14. Although we have successfully employed 
[111In]DTPA-octreotide SPECT/CT (Octreoscan) + a diagnostic CT for diagnosis, staging, and monitoring 
of NET in children and adults15,16, our RDRC approved studies (Figures 3 and 4) as well as comparisons  
of 68Ga-DOTATOC and Octreoscan by European investigators, support our hypothesis that 68Ga- 
DOTATOC will provide at least equivalent, and likely objective improvements in, diagnosis and staging of 
neuroendocrine tumors and other somatostatin receptor positive tumors17-19. Several advantages of 68Ga- 
DOTATOC PET/CT have been pointed out through these published studies. For example, Gabriel and 
colleagues concluded that 68Ga-DOTATOC PET/CT shows a significantly higher detection rate (higher 
sensitivity) compared to conventional Octreoscan SPECT/CT based on a randomized prospective study. 
These findings are corroborated by a prospective study concluding that 68Ga-DOTATOC PET was superior 
to Octreoscan in detection of metastases in the lung, skeleton, liver, and brain10. A study demonstrating 
that 68Ga-DOTATOC PET influences patient management in ≥ 33% of patients further supports the 
introduction of this imaging technique into the United States20. 
 
Comparisons of 
68Ga-DOTATOC and Octreoscan by European investigators support our early 
observations that 68Ga-DOTATOC will provide at least equivalent, and likely objective improvements in, 
diagnosis and staging of NETs17-19. Several advantages of 68Ga-DOTATOC PET/CT have been observed 
through these published studies. For example, Gabriel and colleagues concluded that 68Ga-DOTATOC 
PET/CT shows a significantly higher detection rate (higher sensitivity) compared to conventional 
Octreoscan SPECT/CT based on a randomized prospective study. These findings are corroborated by a 
prospective study concluding that 68Ga-DOTATOC PET was superior to Octreoscan in detection of NET 
metastases in the lung, skeleton, liver, and brain10. A study demonstrating that 68Ga-DOTATOC PET 
influences patient management in ≥ 33% of patients further supports our proposed research20. 
 
VIII. Request for Permission to Charge for an Investigational Drug under an IND 
 
This application is seeking FDA approval to charge for the cost of producing 68Ga-DOTATOC to be used 
as a PET tracer. Costs are justified under Title 21, Chapter 1, Subchapter D Drugs for Human Use, Part 
312, IND application as outlined below: 
 
312.8b (i). 68Ga-DOTATOC PET will be used in this clinical trial as a replacement for Octreoscan 
SPECT imaging.  As stated in our IND application, the primary advantage of Ga-68 based somatostatin 
receptor PET imaging over OctreoScan SPECT is the higher imaging resolution and accurate 
quantitation of uptake due to robust attenuation correction. The improved resolution and quantitation of 
uptake obtained with 68Ga-DOTATOC PET should provide a more accurate assessment of somatostatin 
receptor density, which will lead to a more accurate prediction of treatment response to somatostatin 
analogues. A recent study from Europe comparing 68Ga-DOTATOC with Octreoscan found 68Ga-
DOTATOC to be superior in detection of skeletal and pulmonary involvement of neuroendocrine 
tumors_ENREF_1010. Additional advantages for patients include the lower radiation dose and the shorter 
imaging time. Whereas, Octreoscan uses a 222 MBq imaging dose of Indium (2.8 day half life) resulting 
in an effective dose equivalent (HE) equal to 2.61 rads, 68Ga-DOTATOC (68 min half life) uses 185 MBq 
with an effective dose equivalent of 0.46 rads. In addition, 68Ga-DOTATOC PET/CT can be completed 
within 2 hours compared to an Octreoscan which requires 3 visits over 24 hours, making 68Ga- 
DOTATOC a much more convenient imaging choice for patients. 
 
312.8b (ii). The imaging trial proposed under this IND will enroll up to 200 subjects, ages 6 
months – 100 years of age with Somatostatin receptor positive tumors, many of whom will have had a 
recent Octreoscan and/or high-resolution, contrast-enhanced CT or MRI. The tumor types include 
neuroendocrine tumors, neuroblastoma, medulloblastoma, and pheochromocytoma. The study will thus 
test both efficacy and safety in adults and children with multiple tumor types. 
 
312.8b(iii). 68Ga-DOTATOC will be produced at the University of Iowa PET Center. The 
extraordinary cost of producing 68Ga-DOTATOC precludes performance of the study without charging due 
to manufacturing complexity. The direct costs include purchase and storage of the synthetic peptide, 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
19 
 
 
DOTATOC; a gallium generator every 6 months to produce the short lived isotope; chemicals required in 
the radiolabeling procedure; a specialized ModularLab to ensure reproducibility of the product and 
safety of the radiochemists; single use radiolabeling cassettes to ensure sterility of the product; personnel 
costs for the radiochemists; and the base cost of the PET/CT imaging. 
 
312.8c. As 68Ga-DOTATOC has a 68 minute half-life, it will need to be produced locally when 
trials are expanded to other centers. We intend to provide the protocol as well as all required Standards 
of Procedure associated with this IND to the Society of Nuclear Medicine Clinical Trials Network. We will 
apply for expanded access charging at that time, if appropriate. 
 
Charges will be paid by the subject or the subject’s insurance company with the exception that the scans 
for children < 17 yrs who may be paid from a childhood brain tumor research account in the University of 
Iowa Foundation. 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
20 
 
 
 
IX. References: 
 
1. 
Yao JC, Hassan M, Phan A, et al: One hundred years after "carcinoid": epidemiology of and 
prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Journal of Clinical 
Oncology 26:3063-3072, 2008 
2. 
Rinke A, Muller HH, Schade-Brittinger C, et al: Placebo-controlled, double-blind, prospective, 
randomized study on the effect of octreotide LAR in the control of tumor growth in patients with 
metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 
27:4656-63, 2009 
3. 
Yao JC, Shah MH, Ito T, et al: Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J 
Med 364:514-23, 2011 
4. 
Raymond E, Dahan L, Raoul JL, et al: Sunitinib malate for the treatment of pancreatic 
neuroendocrine tumors. N Engl J Med 364:501-13, 2011 
5. 
Rockall AG, Reznek RH: Imaging of neuroendocrine tumours (CT/MR/US). Best Pract Res Clin 
Endocrinol Metab 21:43-68, 2007 
6. 
Bushnell DL, Baum RP: Standard imaging techniques for neuroendocrine tumors. 
Endocrinol Metab Clin North Am 40:153-62, ix, 2011 
7. 
Kwekkeboom DJ, de Herder WW, van Eijck CH, et al: Peptide receptor radionuclide therapy 
in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 40:78-88 
8. 
Bombardieri E, Ambrosini V, Aktolun C, et al: 111In-pentetreotide scintigraphy: procedure 
guidelines for tumour imaging. Eur J Nucl Med Mol Imaging 37:1441-8, 2010 
9. 
Wild D, Macke HR, Waser B, et al: 68Ga-DOTANOC: a first compound for PET imaging with high 
affinity for somatostatin receptor subtypes 2 and 5. Eur.J.Nucl.Med.Mol.Imaging 32:724, 2005 
10. Buchmann I, Henze M, Engelbrecht S, et al: Comparison of 68Ga-DOTATOC PET and 111In-
DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. 
Eur.J.Nucl.Med.Mol.Imaging. 34:1617-1626, 2007 
11. Reubi JC, Schar JC, Waser B, et al: Affinity profiles for human somatostatin receptor subtypes 
SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur 
J Nucl Med 27:273-82, 2000 
12. Eberlein U, Lassmann M: Dosimetry of [(6)(8)Ga]-labeled compounds. Appl Radiat Isot 76:70-4, 
2013 
13. Shields AF, Lawhorn-Crews JM, Briston DA, et al: Analysis and reproducibility of 3'-Deoxy- 3'-
[18F]fluorothymidine positron emission tomography imaging in patients with non-small cell lung 
cancer. Clin Cancer Res 14:4463-8, 2008 
14. Hofmann M, Maecke H, Borner R, et al: Biokinetics and imaging with the somatostatin receptor 
PET radioligand (68)Ga-DOTATOC: preliminary data. Eur.J.Nucl.Med. 28:1751-1757, 2001 
15. Khanna G, O'Dorisio MS, Menda Y, et al: Gastroenteropancreatic Neuroendocrine Tumors in 
Children and Young Adults. Pediatric Radiology 38:251-259, 2008 
16. O'Dorisio MS, Khanna G, Bushnell D: Combining anatomic and molecularly targeted imaging in the 
diagnosis and surveillance of embryonal tumors of the nervous and endocrine systems in children. 
Cancer Metastasis Review 27:665-677, 2008 
17. Gabriel M, Decristoforo C, Kendler D, et al: 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine 
tumors: comparison with somatostatin receptor scintigraphy and CT. J.Nucl.Med. 48:508- 518, 2007 
18. Jindal T, Kumar A, Venkitaraman B, et al: Role of (68)Ga-DOTATOC PET/CT in the 
evaluation of primary pulmonary carcinoids. Korean J Intern Med 25:386-91, 2010 
19. Jindal T, Kumar A, Kumar R, et al: Role of 68Ga-DOTATOC PET/CT in carcinoids. Pathol Int 
60:143-4, 2010 
20. Ruf J, Heuck F, Schiefer J, et al: Impact of Multiphase 68Ga-DOTATOC-PET/CT on therapy 
management in patients with neuroendocrine tumors. Neuroendocrinology 91:101-9, 2010 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
21 
 
 
 
 
Appendix I 
 
HCCC Clinical Trial Data and Safety Monitoring Plan (DSMP)*  
Date:  4/14/15 
IRB#:  201503708 
Title: Impact of Ga-68 DOTATOC PET-CT Imaging in Management of Neuroendocrine Tumors 
PI:  M Sue O’Dorisio, MD, PhD 
Co-PI: Yusuf Menda, MD 
 
 
 
* All investigator-initiated protocols will be subject to ongoing monitoring of accrual, subject 
eligibility, protocol modifications and continuing reviews.  Active studies will be audited for the 
DSMC by the Clinical Research Safety Officer (CRSO), following guidelines based on level of 
risk to subjects.  Audits will be conducted by reviewing subject files provided by clinical 
research coordinators, as well as original source documentation provided by online medical 
records and research pharmacists.  The CRSO will review adverse events, eligibility of 
subjects, and adherence to the IRB- and PRMC-approved protocol.  Protocols found to have 
discrepancies will be require a response from the PI and an action plan for correcting 
identified deficiencies.  The DSMC will provide a schedule of audit and report dates if 
requested. 
 
 
 
 
 
Type of Clinical Trial: 
 
 Investigator-initiated (UI/HCCC) 
 Investigator-initiated, participating site 
 Pilot study 
 Phase I 
 Phase I/II 
 Phase II 
 Phase III 
 Compassionate-use drug protocol 
 Interventional Treatment 
 Interventional Non-Treatment 
 Non-Interventional 
 
 
 
 
 
 
 
 
 
Study risk-level: 
 
 Level 1—low risk of morbidity or death, * <<1% of death or any adverse event 
 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
22 
 
 
 Level 2—risk of death* <1% or any adverse event 1% – 5% 
 
 Level 3—risk of death* 1% – 5% or grade 4 – 5 SAE 1% – 5% 
 
 Level 4—risk of death* >5% or grade 4 – 5 SAE >15% IND number: 114,398 
 
 Drugs being used on a “compassionate” basis 
 
 
* Risk of death” refers specifically to 100-day treatment-related mortality 
 
 
 
 
Subject inclusion/exclusion Criteria:  
Refer to Section III, page 6 of the protocol  
 
Subject Risks: 
Refer to Section III, pages 8-9 of the protocol  
 
Study Withdrawal/Discontinuation/Stopping Rules: 
Refer to Section III, pages 11-12 of the protocol  
 
Frequently used acronyms:  
 
CRF 
Case Report Form 
CRSO 
Clinical Research Safety Officer 
CTRM 
Clinical Trials Research Manager 
DSMC 
Data and Safety Monitoring Committee  
FDA 
Food and Drug Administration 
HCCC 
Holden Comprehensive Cancer Center 
ICF 
Informed Consent Form 
IND 
Investigational New Drug  
IRB 
Institutional Review Board 
PRMC 
Protocol Review and Monitoring Committee 
 


IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
23 
 
 
Monitoring strategy based on risk-level: 
 
Risk Level 4 
Interventional treatment trials involving investigational agents or devices with a risk of death* >5% or grade 4 – 
5 SAE >15% (all investigator initiated INDs, and most Phase I/II trials, gene therapy, gene manipulation or 
viral vector systems high-risk clinical procedures if performed solely for research purposes.  The use of a new 
chemical or drug for which there is limited or no available safety data in humans. 
An independent Study Monitor or the DSMC Chair (or designee), will review study data (provided by the PI 
and CRSO and communicate with the PI at least quarterly.  A copy of this communication will be forwarded to 
the DSMC and PRMC Chairs.  This communication may coincide with the Clinical Research Safety Officer’s 
(CRSO) quarterly audit when possible.  If an audit has not been conducted—due to lack of research activity--
the quarterly summary letter will occur as scheduled. 
- Subject accrual data will be obtained from OnCore on an ongoing basis by the Clinical Trials Research 
Manager (CTRM) during accrual review for the PRMC. 
- The PI will provide an annual progress report to the DSMC and PRMC. 
- The research coordinator or data manager for the study will register new subjects in OnCore.  A 
scanned copy of the completed eligibility checklist will be attached in OnCore and available for review 
by the CRSO at the time of quarterly audits.  OnCore will send an automatic notification to the CRSO 
when a subject’s status is updated to eligible.  
- Adverse events will be logged in OnCore for review by the CRSO during quarterly audits. Table I below 
provides reporting guidelines for routine adverse event reporting.  
- Serious Adverse Events (SAEs) will be entered directly into an OnCore SAE report by the research 
team.  OnCore will send an automatic notification to the DSMC Chair/acting Chair, CRSO, and CTRM.  
Table II provides reporting guidelines. 
- The CRSO will contact the research team quarterly to coordinate an audit of the trial's research 
records.   Prior to the first audit of a trial the CRSO will schedule a meeting with the PI and/or study 
coordinator, and members of HCCC’s Clinical Research Services.  The purpose of this meeting will be 
to explain the auditing process to the PI/study team and to agree upon key elements of the trial that 
are critical to data integrity, outcome measures, and subject safety.  OnCore auditing functionality will 
be used to conduct, evaluate, and report on each audit. Audits will: 
o verify eligibility of patients accrued to the study, 
o check for the presence of a signed informed consent, 
o determine compliance with protocol’s study plan, 
o determine whether SAEs are being appropriately reported to internal and external regulatory 
agencies,  
o compare accuracy of data in the research record with the primary source documents, 
o review investigational drug processing and documentation, 
o assess cumulative AE/SAE reports for trends and compare to study stopping rules.
Routine Adverse Event Reporting 
Adverse events attributed to the study drug will be reported to the HCCC DSMC via the CRSO following 
established standard operating procedure of the DSMC. 
 
 
Table I:  Routine Reporting of Adverse Events to the CRSO for IND Trials 
 


24 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
Attribution 
Adverse Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Unrelated 
Not required 
Not required 
Not required 
Not required 
CRSO 
Unlikely 
Not required 
Not required 
Not required 
Not required 
CRSO 
Possible 
CRSO 
CRSO 
CRSO 
CRSO 
CRSO 
Probable 
CRSO 
CRSO 
CRSO 
CRSO 
CRSO 
Definite 
CRSO 
CRSO 
CRSO 
CRSO 
CRSO 
 
Adverse Event Reporting Guidelines - This study will use the guidelines developed by the Cancer Therapy 
Evaluation Program (CTEP) for PET and/or SPECT IND agent 
 
 
Expedited Adverse Event Reporting 
Investigators MUST immediately report to the DSMC (via an SAE report in OnCore) any serious adverse 
events (SAE), whether or not they are considered related to the investigational agent(s)/intervention (21 
CFR 312.64). Reporting requirements are in Table II. 
An adverse event is considered serious if it results in ANY of the following outcomes:   
1. Death 
2. A life-threatening adverse event  
3. An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization for ≥ 24 hours  
4. A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions  
5. A congenital anomaly/birth defect.  
6. Important Medical Events (IME) that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon 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. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


25 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
 
Table II: Phase 1 and Early Phase 2 Studies:  Expedited Reporting Requirements for Adverse Events that 
Occur on Studies under an IND within 30 Days of the Last Administration of the Investigational 
Agent/Intervention. 
All serious adverse events must be reported to the DSMC within the timeframes detailed below. 
Hospitalization 
Grade 1 and Grade 2 
Grade 3-5 
Resulting in inpatient hospitalization 
10 calendar days 
1 business day initial;  
5 calendar day report 
Not resulting in inpatient 
hospitalization 
Not required 
Expedited AE reporting timelines are defined as: 
o “1 business day; 5 calendar days” - The AE must initially be submitted electronically using 
OnCore within 1 business day of learning of the SAE, followed by a complete expedited 
report within 5 calendar days of the initial notice. 
o “10 Calendar Days” - A complete expedited report on the AE must be submitted 
electronically within 10 calendar days of learning of the AE. 
Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as 
follows:  
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• 
All Grade 3, 4, and Grade 5 SAEs 
Expedited 10 calendar day reports for: 
• 
Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 
Effective Date:  May 5, 2011 
 
Reporting to the FDA 
It is the responsibility of the IND sponsor-investigator to comply with IND safety reporting as set forth in the 
Code of Federal Regulations, Section 312.32. This responsibility includes providing an annual IND report to 
the FDA. In addition: 
• 
The FDA will be notified via phone (800-332-1088) or fax (800-FDA-0178) within 7 calendar days of 
any SAE that is associated with study treatment, is unexpected, and is fatal or life-threatening. 
• 
The FDA will be notified via fax (800-FDA-0178) or online submission 
(http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM048334.pdf) with a 
MedWatch (3500A or 3500) within 15 calendar days of any SAE that is associated with the study 
treatment, unexpected, and serious but not fatal or life-threatening. This includes any previous SAEs 
that were not initially deemed reportable, but are later determined to meet the criteria for reporting 
(i.e. by the DSMC). 


26 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
 
 
Appendix II 
 
Sample Data Collection Forms 
for 68Ga-DOTATOC PET/CT 


27 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
Patient ID  
 
 
 
 
University of Iowa Hospital  
 
 
 
   
 
INCLUSION 
Inclusion / Exclusion Ga-68 DOTATOC PET Protocol(IMPACT TRIAL)
 
 
1. Y / N 
Age > 6 months 
 
2. Y / N          Histologically diagnosed or suspected (pediatric only)  neuroendocrine  tumor  or  other  
tumor  with  probable somatostatin receptors subtype 2 
 
 
3. Y / N 
Karnofsky performance status or Lansky Play Scale status of > 60 (or 
ECOG/WHO equivalent) 
 
4. Y / N 
Subject  is  male;  or  is  a  female  who  is  either,  surgically  sterile 
(has  had  a documented  bilateral  oophorectomy  and/or  documented  
hysterectomy),  postmenopausal  (>  1 years without menses), ≥60 years 
old, or of childbearing potential for whom a pregnancy test (with the results 
known prior to investigational product administration) is negative. A negative 
pregnancy test will be required for all female subjects with child bearing 
potential. If a false pregnancy test is suspected, e.g., perimenopausal 
condition, an obstetrician will be consulted to determine if she is/is not 
capable of becoming pregnant. Female must also be non-lactating. 
 
EXCLUSION 
 
1. Y / N 
Subject weighs more than 400 pounds. (Subjects who weigh more than 400 
pounds will not be able to fit inside the imaging machines.) 
 
2. Y / N 
Inability to lie still for the entire imaging time (due to cough, severe arthritis, etc.) 
 
3. Y / N 
Inability to complete the needed investigational and standard-of-care imaging 
examinations due to other reasons (severe claustrophobia, radiation phobia, etc.) 
 
4. Y / N 
Does the subject have any additional medical condition, serious intercurrent 
illness, or other extenuating circumstance that, in the opinion of the investigator, 
may significantly interfere with study compliance? 
 
5. Y / N  
Peptide receptor radionuclide therapy (PRRT) within 4 weeks of 
Ga-68 DOTATOC PET/CT scan 
 
 
6. Y / N 
Treatment with Sandostatin LAR within 4 weeks, SQ Octreotide within 12 
hours, or Lanreotide injection within 8 weeks of Ga-68 DOTATOC PET/CT (+/-
5%) 
 
 
 
 
Signature of screening MD 
Date 


28 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
University of Iowa Hospital 
Patient ID  
 
 
 
 
 
 
 
 
 
 
 
 
Data Collection for Imaging Visit 
Subject Data (IMPACT TRIAL) 
 
1) Limited Physical Exam: 
 
Weight _______  Height _______ BP ___/____ RR _______ P_______ Temp _______ 
 
a) HEENT (Circle or fill in blank): 
NORMAL OR  
 
 
b) Chest (Circle or fill in blank): 
NORMAL OR  
 
 
c) Cardiovascular(Circle or fill in blank): NORMAL OR  
 
 
d) Abdomen (Circle or fill in blank): NORMAL OR  
 
 
e) Integument (Circle or fill in blank): 
NORMAL OR  
 
 
f) Musculoskeletal (Circle or fill in blank): NORMAL OR  
 
 
g) Neurological (Circle or fill in blank): NORMAL OR  
 
 
 
 
 
 
 
 
 
Investigator (Signature) 
(Date)   
 


29 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
 
 
 
University of Iowa Hospital  
 
Patient ID:_______________________ 
 
Data Collection for 68Ga-DOTATOC PET/CT(IMPACT TRIAL) 
 
This page will be completed in the PET Center:  Date______________________ 
 
 
1) Pregnancy test (urine) required? Y / N Results_________________  
 
2) Ga-68 DOTATOC Dose:_________mCi @ Injection Time_____:_____  
 
3) Uptake period __________min. 
4) Vital Signs (supine) at PET Completion: P _____, BP ______/______, RR________ Temp ________ °C 
5) Were any adverse events reported or observed since the 68Ga-DOTATOC injection?  
□ No □ Yes 
If yes, provide a narrative of what the patient reported and/or what was observed. 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
________________________________________________________________ 
 
 
Signature of PET staff: __________________________________ Date / Time:  __________________ 


30 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
 
 
University of Iowa Hospital   (IMPACT TRIAL)                                          Patient ID:                                              
 
Karnofsky/Lansky Performance Status 
 
 
This Karnofsky/Lansky performance status is used to determine the functional status of a subject. 
Performance status is a critical data field that has been determined to be essential for all outcome-based 
analyses. The Karnofsky Scale is designed for recipients aged 16 years and older, and the Lansky Scale 
is designed for recipients less than 16 years old. Use this scale to determine the score (10-100) that best 
represents the subject’s activity status at the requested time point. 
 
 
Karnofsky Scale (subject age > 16 years) 
 
Lansky Scale (subject age <16 years) 
Able to carry on normal activity; no special care is 
needed 
Able to carry on normal activity; no special care 
is needed 
100 
Normal, no complaints, no evidence of disease 
90 
Able to carry on normal activity 
80 
Normal activity with effort 
100 
Fully active 
90 
Minor restriction in physically strenuous play 
80 
Restricted in strenuous play, tires more 
easily, otherwise active 
Unable to work, able to live at home cares for 
most personal needs, a varying amount of 
assistance is needed 
Mild to moderate restriction 
70 
Cares for self, unable to carry on normal 
activity or to do active work 
60 
Requires occasional assistance but is able to 
care for most needs 
50 
Requires considerable assistance and frequent 
medical care 
70 
Both greater restrictions of, and less time 
spent in active play 
60 
Ambulatory up to 50% of time, limited active 
play with assistance/supervision 
50 
Considerable assistance required for any 
active play, fully able to engage in quiet play 
Unable to care for self, requires equivalent of 
institutional or hospital care, disease may be 
progressing rapidly 
Moderate to severe restriction 
40 
Disabled, requires special care and assistance 
30 
Severely disabled, hospitalization indicated, 
although death not imminent 
20 
Very sick, hospitalization necessary 
40 
Able to initiate quite activities 
30 
Needs considerable assistance for quiet 
activity 
20 
Limited to very passive activity initiated by 
others (e.g., TV) 
 
 
Signature: 
Date: 
Time:  
 
 
10 
Moribund, fatal process progressing rapidly 
10 
Completely disabled, not even passive play 


31 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
Pp 
 
DOTATOC PET-CT Case Evaluation Pre-Scan        
Patient ID:                                       
I. 
Indication of Ga-68 DOTATOC PET-CT (check one) 
☐Initial staging of pathologically proven NET 
☐Restaging after completion of treatment to detect residual disease 
☐Suspected recurrence of previously treated NET 
☐Monitoring response during therapy of NET 
 
II. YOUR WORKING STAGE FOR THE PATIENT BEFORE Ga-68 DOTATOC PET-CT IS: (check one) 
☐No evidence of disease / In remission 
☐Metastases in multiple sites 
☐Primary disease only / Local recurrence 
☐Metastases with unknown primary 
☐Liver metastases only 
☐Unknown or uncertain 
 
III. 
PRIOR TREATMENT 
Other previous therapy? (check ALL that apply) 
☐Surgery for primary tumor or metastasis 
☐Chemotherapy 
☐External beam radiotherapy 
☐Hepatic directed therapy (SIR-spheres, bland embolization, chemoembolization 
☐PRRT (type__________________________________________) 
☐Octreotide / Lanreotide 
☐None 
 
IV. 
CURRENT TREATMENT 
□ Octreotide LAR or Lanreotide 
□ m-TOR inhibitors (i.e. everolimus) or TK inhibitors (i.e. sunitinib)? 
□ Other chemotherapy___________________________________ 
□ Other treatment______________________________________ 
□ None 
If on treatment, what is your current impression (before PET) of your patient’s response to currently 
ongoing therapy? (check one) 
☐Clearly responding, but uncertain about degree of response 
☐Possible partial response, but uncertain about degree of response 
☐Suspect no response 
☐Suspect progressive disease 
 
V. 
MANAGEMENT / THERAPY 
If 68Ga-DOTATOC PET were not available, your current management strategy would be? (check all that 
apply) 
☐Observation (with close follow-up) 
☐Additional Imaging (CT, MRI) or other non-invasive diagnostic tests 
☐Tissue Biopsy (surgical, percutaneous, or endoscopic) 
☐Octreotide LAR 
☐Surgery for primary tumor / debulking surgery 
☐Liver directed therapy/Liver transplant 
☐PRRT 
☐Chemotherapy or Other Biologic Modifiers (m-TOR inhibitors and/or TK inhibitors) 
□ Palliative External Beam Radiation Therapy 
□ Other Supportive care   
 
 
 
 
Signature: 
Date: 
Time:  
 
 


32 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
Pp 
 
 
DOTATOC PET-CT Case Evaluation Post-Scan     Patient ID_______________________ 
 
 
I. Compared to your Pre-PET assessment, your impression of overall extent of disease is? 
(choose only one) 
☐More extensive 
☐No change 
☐Less extensive 
 
II. Did the PET scan show evidence of cancer activity that was not previously documented? 
☐Yes 
☐No 
 
III. Your Post-PET working clinical staging is: (select only one) 
☐No evidence of disease / In remission 
☐Primary Disease only / Local Recurrence 
☐Liver metastases only 
☐Metastases in multiple sites 
☐Metastatic (distant) with unknown primary 
☐Unknown or uncertain 
 
IV. In light of the PET findings, which of the following management/treatment strategies are 
you now planning or have you already undertaken? (check all that apply) 
☐Observation (with close follow-up) 
☐Additional Imaging (CT, MRI) or other non-invasive diagnostic tests 
☐Tissue Biopsy (surgical, percutaneous, or endoscopic) 
☐Octreotide LAR 
☐Surgery for primary tumor / debulking surgery 
☐Liver directed therapy/Liver transplant 
☐PRRT 
☐Chemotherapy or Other Biologic Modifiers (m-TOR inhibitors and/or TK inhibitors) 
□ Palliative External Beam Radiation Therapy 
□ Other Supportive care 
 
 
 
Signature: 
Date: 
Time:  
 
 
V. Was there a change in management in light of the PET findings? 
☐No Change 
☐Minor Change 
☐Major Change 
 
 
Signature: 
Date: 
Time:  


33 
IND # 114,398 for 68Ga-DOTATOC 
O’Dorisio, M Sue 
Pp 
 
(IMPACT TRIAL)  
Patient ID:__________________ 
 
Ga-68 DOTATOC PET Adverse Event Questionnaire 
Please only list AEs that are new and have happened since the Ga-PET scan. 
POSSIBLE ADVERSE EVENTS 
YES/NO 
COMMENTS/NOTES 
BODY AS A WHOLE 
Pain (abdominal) 
Pain (chest/breast) 
Pain (other/site) 
Fever 
Injection site reaction 
  
CARDIOVASCULAR SYSTEM 
Flushing (vasodilatation) 
DIGESTIVE SYSTEM 
Nausea 
Diarrhea 
Vomiting 
  
RESPIRATORY SYSTEM 
Dyspnea (shortness of breath) 
SKIN & APPENDAGES 
Rash 
Itching (pruritus) 
Hives (urticaria) 
Sweating 
Cyanosis (finger or toe discoloration)  
  
  
CENTRAL NERVOUS 
Visual disturbances 
Numbness of feet 
Numbness of fingers/hands 
Weakness of feet 
Weakness of fingers 
Burning sensation in feet 
Burning sensation in fingers 
  
 
 
Signature:___________________________ Date:________________ Time:____________ 

ICF_000.pdf: 
FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201503708 
APPROVAL DATE: 06/14/18 
EXPIRATION DATE: 09/14/18 
 
 
 
Page 1 of 11 
 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
Impact of Ga-68 DOTATOC PET-CT Imaging in Management of Neuroendocrine 
Tumors  
 
Principal Investigator: 
M. Sue O'Dorisio 
 
Research Team Contact: 
M. Sue O’Dorisio or Yusuf Menda 
 
 
 If you are the parent/guardian of a child under 18 years old who is being invited to be in this study, 
the word “you” in this document refers to your child.  You will be asked to read and sign this 
document to give permission for your child to participate.   
 If you are a teenager reading this document because you are being invited to be in this study, the 
word “you” in this document refers to you.  You will be asked to read and sign this document to 
indicate your willingness to participate. 
 
 
This consent form describes the research study to help you decide if you want to participate.  This form 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights as a research subject.   
 If you have any questions about or do not understand something in this form, you should ask 
the research team for more information.   
 You should discuss your participation with anyone you choose such as family or friends.   
 Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
 
WHAT IS THE PURPOSE OF THIS STUDY? 
 
This is a research study.  We are inviting you to participate in this research study because you have been 
diagnosed with a tumor such as carcinoid, neuroendocrine tumor, neuroblastoma, Ewing’s sarcoma, or 
brain tumor that has cells which carry somatostatin receptors. 
 
The purpose of this research study is to see if your tumor can be identified using a special procedure 
called a positron emission tomography (PET) scan and how the results of this imaging procedure will 
change the management of your tumor. You will have an injection with a radioactive drug called 
68Gallium-DOTA-tyr3-Octreotide (68Ga-DOTATOC) that binds to tumor cells that have somatostatin 
receptors and then have a PET scan. You will then have a "low dose" computed tomography (CT) scan 
immediately after the PET scan on the same scanner.  We believe this special PET/CT scan will be able 
to see smaller tumors than the indium [In-111] pentetreotide scan (Octreoscan™ is the Brand name for 
the scan) that is the current standard of care.   68Ga-DOTATOC is considered investigational, which 
means that it has not been approved by the U.S. Food and Drug Administration. Your physicians will be 
asked to complete a form prior to the scan that summarizes their understanding of the extent of disease 
and the current management of the disease without the information from the PET scan with 68Ga-
DOTATOC. After the scan is completed, they will be asked if and how the scan will impact the 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201503708 
APPROVAL DATE: 06/14/18 
EXPIRATION DATE: 09/14/18 
 
 
 
Page 2 of 11 
management of your tumor.   
 
HOW MANY PEOPLE WILL PARTICIPATE? 
 
Approximately 200 people will take part in this study conducted by investigators at the University of 
Iowa.   
 
HOW LONG WILL I BE IN THIS STUDY? 
 
If you agree to take part in this study, your involvement will include at least 2 visits and a phone call.  
 
If your doctor believes your tumor has progressed or if you receive treatment for your tumor after visit 
2, you may have up to 4 visits and 2 phone calls. You will have an additional visit for a second 68Ga-
DOTATOC PET/CT scan which will include a phone call the following day.This second scan will 
happen only if your doctor believes your tumor has progressed or if you receive treatment for your 
tumor, and a second 68Ga-DOTATOC PET/CT scan is recommended to determine how well your tumor 
responded. Each PET/CT scan will require that you spend approximately 3 hours in the UIHC PET 
Imaging Center.  The screening visit and follow-up visits will take between 30 minutes and an hour. 
 
Pregnancy Testing for Females Under the Age of 18 
 
All females who are physically able to become pregnant will be required to have a pregnancy test before 
each PET scan. If the test shows that you are pregnant, you will not be able to continue in the study. This 
testing will occur in a private area without any of your family members with you.  
 
If you are 12 years of age or older we will only tell you the results of the test.  
 
You can decide whether or not to tell your parents or guardian the results of the pregnancy test, 
however, if you are pregnant we will need to tell your parents you cannot continue in the study. 
If the pregnancy test shows that you are pregnant we will ask you whether or not you want us to talk 
with your parents or guardian about your pregnancy.  
 
If you are under 12 years of age and the pregnancy test shows that you are pregnant, we are required to 
report the pregnancy to the proper authorities.  
  
IMPORTANT: No matter how old you are - if we think that your pregnancy may have happened 
because of abuse, we will tell the proper authorities and your parents or guardian will be told about your 
pregnancy. 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201503708 
APPROVAL DATE: 06/14/18 
EXPIRATION DATE: 09/14/18 
 
 
 
Page 3 of 11 
WHAT WILL HAPPEN DURING THIS STUDY? 
On the initial visit, we will describe the study to you, answer your questions regarding the study and will 
perform a physical exam.  
• 
Visit One in Holden Comprehensive Cancer Center or Pediatric Specialty Clinic 
(approximately 30 min to 1 hour) 
• 
Obtain consent 
• 
Review pathology report with diagnosis of tumor 
• 
Review previous conventional imaging such as Octreoscan™ or high-resolution, 
contrast-enhanced CT or MRI showing uptake in tumor or metastatic lesion 
• 
Record height, weight, blood pressure, heart rate, respirations, temperature, physical 
exam 
• 
Evaluate functional status 
• 
Have blood drawn for pregnancy test if you are of childbearing potential – if clinical 
routine blood testing is needed this will be at the same time  
 
If review of this information determines you are eligible to continue, you will continue in the study. 
 
• 
Visit Two in the PET Imaging Center (this visit may be combined with Visit One and occur 
on the same day as Visit One); will take approximately 3 hours 
• 
Record height and weight 
• 
Have urine pregnancy test if you are of childbearing potential, not required if a negative 
serum/urine pregnancy test within one day (which may have been obtained on your first 
visit).  
• 
We may give you a medicine, alprazolam (Xanax®) or  lorazepam (Ativan®) at least 30 
minutes before the PET scan to help you relax  
• 
Have an intravenous catheter (IV) inserted 
• 
Receive IV bolus injection of 68Ga-DOTATOC over less than 1 minute  
• 
Wait approximately 1 hour for the distribution of 68Ga-DOTATOC in your body 
• 
Have PET/CT scan over approximately 30 minutes  
• 
Record blood pressure, heart rate, respirations, temperature and assess for adverse events 
prior to discharge from PET Center (approximately 10-15 min) 
 
• 
Phone call to you at your home or on your cell phone the next day: 
• 
Discuss any side effects or reactions to PET scans (rash, nausea, headache, fatigue) 
• 
Answer any questions you may have regarding the study 
 
Visits three and four will happen only if your doctor believes your tumor has progressed or if 
you receive treatment for your tumor, such as surgery, liver embolization, peptide receptor 
radiotherapy (PRRT), chemotherapy, biological therapy or radiation therapy and your doctor 
needs to re-evaluate the tumor status. The second scan must be between 6 – 18 months after 
the Visit 2 (scan 1). 
 
• 
Visit Three in Holden Comprehensive Cancer Center (Optional; 6-18 months after the 1st 
scan); will take approximately 30 min to 1 hour 
• 
Review your history of symptoms, biomarkers, any Octreoscan™ and high-resolution, 
contrast-enhanced CT or MRI, and any treatment received. 


FOR IRB USE ONLY 
APPROVED BY: IRB-01 
IRB ID #: 201503708 
APPROVAL DATE: 06/14/18 
EXPIRATION DATE: 09/14/18 
 
 
 
Page 4 of 11 
• 
Record height, weight, blood pressure, heart rate, respirations, temperature, physical 
exam 
• 
Have blood drawn for pregnancy test if you are of childbearing potential – if clinical 
routine blood testing is needed this will be done at the same time  
• 
Evaluate functional status 
 
 
• 
Visit Four in the PET Imaging Center  (Optional)  - (this visit may be combined with Visit 
Three and occur on the same day as Visit Three), will take approximately 3 hours 
• 
Record height and weight 
• 
Have pregnancy test if you are of childbearing potential, not required if a negative serum 
test within 24 hours of PET scan 
• 
We may give you a medicine, alprazolam (Xanax®) or  lorazepam (Ativan®) 30 minutes 
before the PET scan to help you relax  
• 
Have an IV inserted 
• 
Receive IV bolus injection of 68Ga-DOTATOC over less than 1 minute  
• 
Wait approximately 1 hour for the distribution of 68Ga-DOTATOC in your body 
• 
Have PET/CT scan approximately 30 minutes  
• 
Record blood pressure, heart rate, respirations, temperature and assess for adverse events 
prior to discharge from PET Center (approximately 10-15 min) 
 
• 
Phone call to you at your home or on your cell phone (Optional) 
• 
Discuss any side effects or reactions to PET scans (rash, nausea, headache, fatigue) 
• 
Answer any questions you may have regarding the study 
 
The PET/CT images for this study will be reviewed by a nuclear medicine physician and will be entered 
in your medical record.  
 
The following information will be obtained from your medical record: pathology report indicating 
presence of a tumor; biomarkers that indicate whether your tumor is growing, including any blood work,  
CT or MRI and an Octreoscan™ showing this tumor, and what treatments you may have had since your 
last Octreoscan™ and CT or MRI. 
 
There are no further research procedures in this study after you complete the 68Ga-DOTATOC scans 
and follow-up phone call. We will follow-up your clinical progress from your clinical chart up to 5 years 
after your 68Ga-DOTATOC PET/CT scan. If you do not receive your follow-up care at the University, 
we may contact you to ask for the follow-up information. At that time, if you allow us, we may also 
contact your physician to obtain information on your tumor therapy/follow-up.    
 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study. 
 
There is a small risk of pain, burning, or infection at the site of the blood draws for laboratory tests and 


FOR IRB USE ONLY 
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at the site of IV injection of Ga-68 DOTATOC. If you elect to take alprazolam or lorazepam prior to the 
PET/CT scan, you may experience drowsiness or unclear thinking.  You will not be allowed to drive or 
to operate machinery for 12-24 hrs. after receiving alprazolam or lorazepam.  You will need a driver to 
take you home or to your hotel following either of these two drugs. Children may require sedation or 
anesthesia to remain still during the PET scanning procedure. The risks of sedation include a reaction to 
the medication used for sedation or anesthesia. If anesthesia is required, there is a risk of injury to the 
throat or airways from insertion of the breathing tube.  
 
There is a financial risk to participating in this study. The FDA has previously allowed us to charge the 
patient or his/her insurance company for the cost of the drug, which is prepared in the UIHC PET 
Center. The charge to the patient or her/his insurance company is $5,915. The other costs to the patient 
for being in this study include travel and loss of work hours; each subject will be free to decline 
participation based on these financial issues. 
 
There may be some emotional/psychological risk of the PET scan showing more widespread tumor than 
was previously recognized; however, there is also the possibility that the scan will show less tumor than 
previously thought. 
 
 Radiation Risk 
The maximum amount of radiation from the research-related radiation procedures in this study is 
equivalent to approximately 60  % of the annual radiation limit for a medical worker. Long term effects 
on your health such as cancer cannot be ruled out from this amount of radiation.  This dose estimate 
takes into account only the exposure to research procedures in this project.  If you have participated in 
other research studies involving radiation exposure, you should be aware that the risk of effects from 
radiation is believed to increase with each exposure you receive (including studies performed as part of 
your medical care).  
PET Scan Risk 
The PET/CT scanner is a large machine with a hollow tube that will be used to see how much 68Ga-
DOTATOC is taken into your tumor. You will be asked to lie on your back on a special table that slides 
into the tube.  The sides of the tube will be fairly close to your body and you will be in this scanner for 
approximately 30-35 minutes.  We will monitor you closely while you are inside the scanner. You will 
also be given a call button to press if you would need to speak to us during the scan. The risks from the 
PET scan include the radiation described above, pain from lying still on the table or a panic attack if you 
have claustrophobia. 
 
Children may require sedation or anesthesia to remain still during the PET scanning procedure.  The 
risks of sedation include a reaction to the medication used for sedation or anesthesia.  If anesthesia is 
required, there is a risk of injury to the throat or airways from insertion of the breathing tube. 
 
Women Capable of Becoming Pregnant 
If you are a woman who is capable of becoming pregnant, we will ask you to have a pregnancy test 
before beginning this study.  You must use effective birth control methods and try not to become 
pregnant while participating in this study.  If you become pregnant, there may be unknown risks to your 
fetus, or risks to your fetus that we did not anticipate, associated with being in the study. There may be 
long-term effects of the treatment being studied that could increase the risk of harm to an unborn child.  
If you believe or know you have become pregnant while participating in this research study, please 


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contact Dr. MS O’Dorisio at 319-356-3595 as soon as possible so that counseling can be provided to 
you.  If a false positive pregnancy test is suspected, an obstetrician will be available to help you and the 
study team determine if you are or are capable of becoming pregnant.    
 
Radiation Exposure in Women Capable of Becoming Pregnant 
You may not participate in this study if you are pregnant.  If you are capable of becoming pregnant, we 
will perform a pregnancy test before exposure to research-related radiation.  You must tell us if you may 
have become pregnant within the previous 14 days because the pregnancy test is unreliable during that 
time. 
 
Radiation Exposure in Women Who are Breast Feeding 
You may not participate in this study if you are breast feeding an infant.  There is a chance that the 
68Ga-DOTATOC could travel to your infant in your breast milk and cause unknown risks to your child. 
 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
 
We don’t know if you will benefit from being in this study.  We may be able to see more tumor lesions 
(or less) compared to an Octreoscan™.  If you receive a second 68Ga-DOTATOC PET/CT scan 12-36 
months after your first, we may or may not be able to determine how much response you had to the 
treatment. 
 
However, we hope that, in the future, other people might benefit from this study because of knowledge 
gained in determining whether 68Ga-DOTATOC PET/CT scans are more sensitive than the current 
Octreoscan™ plus high-resolution, contrast-enhanced CT for detecting somatostatin receptor positive 
tumors and measuring response to treatment. 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
 
You will have additional costs associated with being in this research study. You will be required to pay 
for study procedures that are not part of your regular care. This includes $5,915 for the 68Ga-
DOTATOC PET/CT scan and associated costs, and pregnancy testing (if needed). The $5,915 charge 
includes making the drug, performing the PET/CT, interpreting the results, and sending a report to your 
doctor.  
 
In some cases, insurance may cover part of the study procedures. It is recommended that you contact 
your insurance provider in advance to determine if payment for the study procedures will be covered. In 
the event that your insurance company denies all or part of the study procedures as “non-covered,” you 
will be responsible for the charges. The University of Iowa Hospitals & Clinics has developed a plan for 
helping you obtain insurance coverage.  If necessary, a physician will engage in a peer-to-peer review 
with your insurance company.  This will increase the chances of the costs being covered, but does not 
guarantee coverage.  If the insurance company denies this request, you will be informed of the cost.  
You may choose to pay or decline to participate in the study.  
 
Medicare cannot be billed for study procedures that are not part of your regular care. If you have 
Medicare, you will be billed for all study procedures not part of your regular care. 


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If you are a child with a tumor, study procedures may be paid by either the University of Iowa Tim 
Dwight Foundation or the University of Iowa Research for the Kids fund. Talk to your study doctor to 
determine if you may qualify. 
 
  
 
In addition, you will be responsible for your travel costs.   
 
You and/or your medical/hospital insurance carrier will remain responsible for your regular medical care 
expenses, including any biomarker blood tests and other imaging studies.  
 
 
WILL I BE PAID FOR PARTICIPATING? 
 
You will not be paid for being in this research study.   
  
WHO IS FUNDING THIS STUDY? 
 
The University and the research team are receiving no payments from other agencies, organizations, or 
companies to conduct this research study. 
 
The University of Iowa Neuroendocrine Tumor Fund in addition to the University of Iowa Tim Dwight 
Pediatric Brain Tumor Fund are funding this research study.  This means that the University of Iowa is 
receiving payments from the University of Iowa Neuroendocrine Tumor Fund and the University of 
Iowa Tim Dwight Foundation to support the activities that are required to conduct the study.  No one on 
the research team will receive a direct payment or increase in salary from the University of Iowa 
Neuroendocrine Tumor Fund or the University of Iowa Tim Dwight Foundation for conducting this 
study. 
 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
 If you are injured or become ill from taking part in this study, medical treatment is available at the 
University of Iowa Hospitals and Clinics. 
 The University of Iowa does not plan to provide free medical care or payment for treatment of any 
illness or injury resulting from this study unless it is the direct result of proven negligence by a 
University employee.  
 If you experience a research-related illness or injury, you and/or your medical or hospital insurance 
carrier will be responsible for the cost of treatment. 
 
WHAT ABOUT CONFIDENTIALITY? 
 
We will keep your participation in this research study confidential to the extent permitted by law.  
However, it is possible that other people such as those indicated below may become aware of your 
participation in this study and may inspect and copy records pertaining to this research.  Some of these 
records could contain information that personally identifies you.  


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 federal government regulatory agencies, including the U.S. Food and Drug Administration,    
 auditing departments of the University of Iowa, and  
 the University of Iowa Institutional Review Board (a committee that reviews and approves 
research studies)  
 
In the future, the U.S. Food and Drug Administration may continue to use your health information that is 
collected as part of this study.  The FDA may combine information from this study with the results of 
other studies to re-analyze the safety and effectiveness of the Ga-DOTATOC PET/CT in the diagnosis, 
staging, or evaluation of response of tumors such as yours. 
 
To help protect your confidentiality, we will keep all of your health information related to this study in a 
file that is in a locked cabinet inside a locked room in UIHC.  Data related to the PET scans will be kept 
in a secure archive that can only be accessed with a special identification and password. If we write a 
report or article about this study or share the study data set with others, we will do so in such a way that 
you cannot be directly identified. 
 
The University of Iowa Hospitals and Clinics generally requires that we document in your medical 
record chart that you are participating in this study. The information included in the chart will provide 
contact information for the research team as well as information about the risks associated with this 
study. We will keep this Informed Consent Document in our research files; it will not be placed in your 
medical record chart. 
  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  This website will not include information that can identify you.  At most, the website will include 
a summary of the results.  You can search this website at any time. 
  
WILL MY HEALTH INFORMATION BE USED DURING THIS STUDY? 
 
The Federal Health Insurance Portability and Accountability Act (HIPAA) requires your health care 
provider to obtain your permission for the research team to access or create “protected health 
information” about you for purposes of this research study.  Protected health information is information 
that personally identifies you and relates to your past, present, or future physical or mental health 
condition or care.  We will access or create health information about you, as described in this document, 
for purposes of this research study.  Once your health care provider has disclosed your protected health 
information to us, it may no longer be protected by the Federal HIPAA privacy regulations, but we will 
continue to protect your confidentiality as described under “Confidentiality.” 
 
We may share your health information related to this study with other parties including federal 
government regulatory agencies, the University of Iowa Institutional Review Boards and support staff.  
 
You cannot participate in this study unless you permit us to use your protected health information.  If 
you choose not to allow us to use your protected health information, we will discuss any non-research 
alternatives available to you.  Your decision will not affect your right to medical care that is not 
research-related.  Your signature on this Consent Document authorizes your health care provider to give 
us permission to use or create health information about you. 
 


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Although you may not be allowed to see study information until after this study is over, you may be 
given access to your health care records by contacting your health care provider. Your permission for us 
to access or create protected health information about you for purposes of this study has no expiration 
date. You may withdraw your permission for us to use your health information for this research study by 
sending a written notice to M. Sue O’Dorisio, MD, PhD, 200 Hawkins Drive, Iowa City, IA 52242.  
However, we may still use your health information that was collected before withdrawing your 
permission.  Also, if we have sent your health information to a third party, such as the U.S. Food and 
Drug Administration, or we have removed your identifying information, it may not be possible to 
prevent its future use.  You will receive a copy of this signed document. 
 
 
IS BEING IN THIS STUDY VOLUNTARY? 
 
Taking part in this research study is completely voluntary.  You may choose not to take part at all.  If 
you decide to be in this study, you may stop participating at any time.  If you decide not to be in this 
study, or if you stop participating at any time, you won’t be penalized or lose any benefits for which you 
otherwise qualify. 
 
What if I Decide to Drop Out of the Study? 
If you decide to leave the study early, we will ask you to contact a member of the study team (Names 
and phone numbers are listed on the front of this consent form). We will ask your reason for dropping 
out to determine if there are any adverse events that have not been reported. 


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Will I Receive New Information About the Study while Participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can Someone Else End my Participation in this Study? 
Under certain circumstances, the researchers might decide to end your participation in this research 
study earlier than planned.  This might happen because your disease flares and you require a large dose 
of Sandostatin to relieve your symptoms, in which case it would not be safe for you to continue.  We 
would also end your participation if you became pregnant. 
 
WHAT IF I HAVE QUESTIONS? 
 
We encourage you to ask questions.  If you have any questions about the research study itself, or if you 
experience a research-related injury, please contact Dr. O’Dorisio at 319-356-3595.  
 
If you have questions, concerns, or complaints about  your rights as a research subject or about research 
related injury, please contact the Human Subjects Office, 105 Hardin Library for the Health Sciences, 
600 Newton Rd, The University of Iowa, Iowa City, IA  52242-1098, (319) 335-6564, or e-mail 
irb@uiowa.edu.  General information about being a research subject can be found by clicking “Info for 
Public” on the Human Subjects Office web site, http://hso.research.uiowa.edu/. To offer input about 
your experiences as a research subject or to speak to someone other than the research staff, call the 
Human Subjects Office at the number above. 
 
 
This Informed Consent Document is not a contract. It is a written explanation of what will happen 
during the study if you decide to participate. You are not waiving any legal rights by signing this 
Informed Consent Document. Your signature indicates that this research study has been explained to 
you, that your questions have been answered, and that you agree to take part in this study.  You will 
receive a copy of this form. 
 
 
Subject's Name (printed):  __________________________________________________________ 
 
 
Do not sign this form if today’s date is on or after EXPIRATION DATE: 09/14/18. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Subject)  
 
 
 
 
(Date) 
 


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Parent/Guardian Name and Relationship to Subject: 
 
 
__________________________________________ 
_______________________________ 
(Name - printed) 
 
 
 
 
 
(Relationship to Subject - printed) 
 
 
Do not sign this form if today’s date is on or after EXPIRATION DATE: 09/14/18. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Parent/Guardian) 
 
 
 
(Date)  
 
 
 
 
 
Statement of Person Who Obtained Consent 
 
I have discussed the above points with the subject or, where appropriate, with the subject’s legally 
authorized representative.  It is my opinion that the subject understands the risks, benefits, and 
procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date)