Clinical trial NCT03602911
Conditions: Head and Neck Squamous Cell Carcinoma
Sponsor: West Virginia University
Start date: 2019-02-01; Completion date: 2021-04-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a proof-of-concept trial to compare 18F-FDG-PET/CT with NETSPOT (68Ga-DOTA-TATE), a commercially available radiotracer packet that utilizes 68Ga to image SSTR-specific tissue.

Detailed description:
Patients meeting inclusion criteria will be consented at the time of scheduling. All patients will undergo 18F-FDG-PET/CT per established protocol. Following 18F-FDG-PET/CT, the patient will undergo NETSPOT imaging with the AAA-provided dose. These scans will be performed no less than 8 hours, no more than 7 days apart. For patients undergoing same-day imaging, NETSPOT imaging will be performed prior to 18F-FDG-PET/CT. Following imaging, both 18F-FDG-PET/CT and NETSPOT imaging will be compared by trained neuroradiologists for SUV values and concordance with known sites of disease. Biopsies will be performed as is standard to verify all sites of primary or metastatic disease. Patients with oropharyngeal tumors will have HPV testing performed via the standard of care surrogate marker p16. Patients with p16-positive tumors will be recorded and analyzed separately for the above measures. Patients will be followed for a total of 1 year after the study and outcomes of overall survival, disease-free survival, presence and site of recurrence and development of metastatic disease will be recorded. All gathered data will be compared between reported 18F-FDG-PET/CT and NETSPOT imaging for true positive, true negative, positive predictive value and negative predictive value of patient groups.

Arms: arm 1: The isotope 68Ga, available as NETSPOT and 18F-FDG-PET/CT per established protocol will both be administered
Interventions: intervention 1: The isotope 68Ga, NETSPOT and 18F-FDG-PET/CT
Intervention descriptions: intervention 1: All patients will undergo 18F-FDG-PET/CT per established protocol. Following 18F-FDG-PET/CT, the patient will undergo NETSPOT imaging

Protocol documents:
Prot_SAP_003.pdf: 
 
 
 
 
Title: To evaluate the utility of NETSPOT Imaging in Head and Neck Cancer Patients 
Date: December 28, 2017 
NCT# NCT03602911 


 
 
 
 
 
Investigator Initiated Study Proposal 
Proposed Study Title 
Study Title: 
To evaluate the utility of NETSPOT Imaging in Head and Neck Cancer Patients 
Request Date: 
12/28/2017 
Principal Investigator Contact Information 
Name: 
Rusha Patel 
Title: 
MD 
Address 
1 Medical Center Drive 
City, State, Zip 
Morgantown, WV 26506 - 9200 
Phone: 
304-293-3457 
E-mail: 
Rusha.patel@hsc.wvu.edu 
Contracting Information (if applicable) 
Name: 
Phone/Fax: 
E-mail: 
Study Information 
Indication: 
Enrollment criteria include all patients with head and neck cancer undergoing 18F FDG 
PET/CT at time of primary diagnosis or after completion of therapy. 
Line of treatment: 
Phase: 
Preliminary 
Number of Subjects: 
30 


Background and Rationale: 
Provide background (including references) on unanswered question(s) the study is attempting to answer 
Head and neck squamous cell carcinoma (HNSCC) makes up 90% of head and neck cancers. The incidence is increasing, 
in part due to the human papilloma virus (HPV), a well-established factor in the development of HNSCC. Unfortunately, 
tumor-specific imaging for HNSCC and HPV-related HNSCC are non-existent, making detection and follow-up reliant on 
surrogate markers for metabolic activity. 18F FDG Positron Emission Tomography (PET), combined with computerized 
tomography (PET/CT), is the current standard for imaging in HNSCC. Specifically, 18F FDG PET/CT is used for patients with 
advanced stage disease, those with unknown primary site, and as part of the post-treatment imaging. 18F FDG PET/CT 
has a high sensitivity, but the specificity can be limited in pateints with underlying inflammation, infection, or after 
radiation therapy. As such, tumor-specific imaging has the potential to improve detection of de novo and/or recurrent 
tumors in this high risk population. 
Interestingly, HNSCCs have been found to express somatostatin receptors (SSTRs). SSTRs have also been found in 
laryngeal cancer specimens and cancers of the oral cavity and oropharynx, but not in control tissue1,2. Recent studies 
have found that HPV causes mutations in the same pathways that activate SSTR expression on tumor cells3. These 
studies suggest a correlation with HPV-positive HNSCC and SSTR expression. This latter group of patients often have 
non-detectable primary tumors that arise from the oropharynx, an area that normally exhibits 18F FDG PET/CT uptake 
thus making tumor localization difficult. Schartinger et al studied SSTR PET/CT in a small series of HNSCC patients and 
found that all patients showed radionucleotide uptake on imaging4. Multiple case reports have been published showing 
similar uptake for head and neck squamous cell carcinomas by 68Ga5,6. An unpublished trial was performed comparing 
SSTR PET/CT with 18F FDG PET/CT for 35 patients with HNSCC; the study concluded that SSTR PET/CT had the potential 
to be more specific for HNSCC than 18F FDG PET/CT7. Unfortunately the study was small, HPV status was not correlated, 
and recurrent/post-treatment patients were not studied. These studies show that SSTR-specific imaging, such as 
NETSPOT, has the potential to be equal to and possibly more specific than 18F FDG PET/CT for HNSCC patients, especially 
in the setting of HPV positivity, unknown primary site tumors, and post-treatment follow-up. More importantly, a 
therapeutic target for SSTRs is widely available; as such, HNSCC patients who show clinical updake on NETSPOT imaging 
may be candidates for future studies using targeted therapeutics. 
Objectives and study aims: 
List the primary/secondary objectives to correspond directly with the listed hypotheses; define the role of AAA 
compounds 
Study Aim: 
Evaluate utility of NETSPOT imaging for disease detection in HNSCC, as well as the potential for targeted receptor- 
specific therapeutics. 


Primary Objectives: 
To determine the utility of NETSPOT imaging, as compared to 18F FDG PET/CT, in detection and staging of HNSCC. 
To evaluate the potential of NETSPOT imaging in guiding the use of targeted radiopeptides for HNSCC treatment. 
Secondary Objectives: 
To determine if NETSPOT imaging and 18F FDG PET/CT, when used together, can lead to improved tumor delineation and 
detection of metastatic disease. 
To determine the imaging charactersistics of NETSPOT versus 18F FDG PET/CT in the setting of inflammation. 
To determine if NETSPOT imaging uptake correlates with tumor HPV-positivity. 
To determine if patients with tumor uptake on NETSPOT imaging exhibit different disease outcomes than patients 
without uptake. 
Hypothesis: 
List the clinical hypotheses in order of priority 
NETSPOT imaging will be at least equivalent to 18F FDG PET/CT in the detection and staging of HNSCC. 
The combination of NETSPOT imaging and 18F FDG PET/CT, will have increased specificity for detecting the primary site 
for HNSCC of unknown primary than 18F FDG PET/CT alone. 
The combination of NETSPOT imaging and 18F FDG PET/CT, will have increased specificity for detecting disease 
recurrence and metastasis following treatment than 18F FDG PET/CT alone. 
Is a study protocol already available (Yes/No)? If yes, please attach to the IIS form 
No. 
Study Design/Clinical Plan: 
Provide a concise overview stating the type of experimental design (for ex, randomized/non-randomized, condensed 
eligibility criteria etc) 
Design: This study will be designed as a “proof-of-concept” trial to compare NETSPOT with 18F FDG PET/CT for HNSCC. 
Inclusion Criteria: 


HNSCC patients undergoing planned 18F FDG PET/CT at time of primary diagnosis. 
HNSCC patients undergoing planned 18F FDG PET/CT for unknown primary site. 
HNSCC patients undergoing planned 18F FDG PET/CT after completion of adjuvant treatment. 
Exclusion Criteria: 
Inability to undergo 18F FDG PET/CT imaging due to medical comorbidities. 
Enrollment: 
Patients meeting inclusion criteria will be enrolled on evaluation. Based on our current clinical volume, we plan to enroll 
30 patients over a 6 month time frame. 
Preliminary analysis (outlined below) will be done after the first 30 patients to assess the utility of NETSPOT imaging in 
HNSCC. 
Treatment: 
List the clinical dosage/dosage form, route, and dose regimen 
Brief Overview: 
Patients meeting inclusion criteria will be consented at the time of scheduling. 
All patients will undergo 18F FDG PET/CT per established protocol. 
Following 18F FDG PET/CT, the patient will undergo NETSPOT imaging with the AAA-provided dose. These scans will be 
performed no less than 24 hours, no more than 7 days apart. 
Analysis: 
Both 18F FDG PET/CT and NETSPOT images will be reviewed by the senior radiatiologist and the primary surgeon for 
concordance between images. SUV will be measured for both images and recorded. 
Patients will undergo clinical follow-up based on 18F FDG PET/CT results as per protocol. 
True positive results will be recorded for both 18F FDG PET/CT and NETSPOT images and analyzed for sensitivity and 
specificity. 
For patients undergoing surgical treatment, pathology results including routinely reported HPV markers will be recorded 
and compared to NETSPOT imaging characteristics. 


Follow-up 
All enrolled patients will be followed for 1 year after imaging. 
Expected Results/Outcomes: 
We expect that 18F FDG PET/CT and NETSPOT will have similar uptake and specificity for primary tumor. We hypothesize 
that NETSPOT will have increased specificity for unknown primary site tumor and recurrent or metastatic disease. 
Finally, we hope that NETSPOT positivity in HNSCC will allow for future study of targeted radionuclide therapies for 
HNSCC. 
Applicability of Results: 
Any other information regarding the medical need and/or the strategic importance of the research which may help the 
committee’s evaluation 
A proof-of-concept trial to compare SSTR/ PET/CT with 18F FDG PET/CT in the head and neck cancer population would be 
a novel use of the NETSPOT technology. The study is warranted based on past data and the potential for success, 
especially in patients with oropharyngeal tumors, previous radiation or inflammatory disease; all of whom 18F FDG 
PET/CT is difficult to interpret. If the hypothesis is supported, Advanced Accelerator will have a new application for the 
NETSPOT technology and a new area for business development and revenue. 
Additional Research (if applicable): 
Histology, biomarkers, PK etc. 
Statistical Plan: 
Include justification for clinical sample size and primary hypothesis testing 
Statistical Considerations: 


The primary objective of this study is to evaluate SSTR receptor expression in the head and neck cancer population. The 
secondary objective is to assess the concordance based on SSTR PET/CT with and without FDG PET/CT outcomes. 
A Student t-test will be used to assess the difference of SSTR expression between the diagnostic results (positive vs 
negative) and Fisher’s exact test will be used to assess the association between dichotomized expression (high vs low) 
and a binary outcome (positive vs negative). The sensitivity will be estimated by a proportion of true positives that are 
correctly identified by the new method. The specificity will be estimated by a proportion of true negative that are 
correctly identified by the new method. The corresponding 95% confidence intervals will be estimated based on 
binomial distributions. 
Sample Size: Based on the two-sided t-test, a sample size of 30 will have 81% power to detect 0.95 standard deviations 
of the SSTR expression between positive and negative outcomes (15 per group) at a 0.10 significance level. In addition, 
based on the historical data and current literatures, head and neck squamous cell carcinoma (HNSCC) makes up 90% of 
head and neck cancers. For primary tumor detection, 18F FDG PET/CT is about 96% sensitive (oral cavity only) and 
anywhere from 91%-98% accurate at detecting lymph node metastasis, with sensitivity of 67%-79%, and specificity of 
82-95%. For detecting recurrent disease, 18F FDG PET/CT is ranged from 83%-100% sensitive and 90-98% specific. Based 
on one-sided non-inferiority test for two correlated proportions with a concordance of 0.90, when the maximum 
allowable difference between these proportions that still results in non-inferiority (the range of non-inferiority) is 0.15, 
a sample size of 30 subjects achieves 81% power at a significance level of 0.10. 
 

ICF_004.pdf: 
Human Research Protocol 
Only Minimal Risk Consent Form 
(With HIPAA) 
Chestnut Ridge Research Building 
886 Chestnut Ridge Road 
PO Box 6845 
Morgantown, WV 26506-6845 
P a g e | 1 
Phone: 304-293-7073 
Fax: 304-293-3098 
http://oric.research.wvu.edu 
Subject’s 
Initials 
 
Date 
 
 
 
 
 
Title: Comparison of NETSPOT Imaging Vs F FDG PET/CT in Head & Neck Cancer Patients 
NCT#  NCT03602911 
Date: December 28, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Human Research Protocol 
Only Minimal Risk Consent Form 
(With HIPAA) 
Chestnut Ridge Research Building 
886 Chestnut Ridge Road 
PO Box 6845 
Morgantown, WV 26506-6845 
P a g e | 2 
Phone: 304-293-7073 
Fax: 304-293-3098 
http://oric.research.wvu.edu 
Subject’s 
Initials 
 
Date 
 
 
 
 
 
 
Only Minimal Risk 
Consent Information and HIPAA Form 
Principal Investigator 
Rusha Patel, MD 
Department 
Otolaryngology 
Protocol Number 
1804059675 
Study Title 
Comparison of NETSPOT Imaging Vs F FDG PET/CT in Head & Neck Cancer Patients 
Co-Investigator(s) 
Gary Marano, MD 
Sponsor (if any) 
Advanced Accelerator Applications USA Inc. 
 
 
Contact Persons 
 
 
In the event you experience any side effects or injury related to this research, you should contact Rusha Patel, MD at 
(304)293-3457 (After hours contact: Rusha Patel, MD by contacting the ENT resident on call at (304) 598-4000 ). If you 
have any questions, concerns, or complaints about this research, you can contact Dr. Patel at (304) 293-3457. 
 
For information regarding your rights as a research subject, to discuss problems, concerns, or suggestions related to the 
research, to obtain information or offer input about the research, contact the Office of Research Integrity and 
Compliance at (304) 293-7073. 
In addition if you would like to discuss problems, concerns, have suggestions related to research, or would like to offer 
input about the research, contact the Office of Research Integrity and Compliance at 304-293-7073. 
Introduction 
You,  
, have been asked to participate in this research study, which has been explained to you 
by  
 
. This study is being conducted by Rusha Patel, 
MD, in the Department of Otolaryngology at West Virginia University with support provided by Advanced Accelerator 
Applications USA Inc. 
 
Purpose(s) of the Study 


Human Research Protocol 
Only Minimal Risk Consent Form 
(With HIPAA) 
Chestnut Ridge Research Building 
886 Chestnut Ridge Road 
PO Box 6845 
Morgantown, WV 26506-6845 
P a g e | 3 
Phone: 304-293-7073 
Fax: 304-293-3098 
http://oric.research.wvu.edu 
Subject’s 
Initials 
 
Date 
 
 
 
NETSPOT is a radioactive diagnostic agent for PET scan imaging to identify neuroendocrine tumors (NET) in adult and 
pediatric patients. NETSPOT obtained FDA approval in 2016. Prior to this, three large studies examined the safety of 
NETSPOT imaging in NET patients; these studies found no adverse side effects and that NETSPOT was a useful imaging 
modality in this group of patients. Similar studies have suggested that NETSPOT imaging may have a role in head and 
neck cancer; however it is not currently FDA approved for this indication. For this study we would like to determine the 
usefulness of NETSPOT imaging for detection of Head & Neck cancer as well its potential for therapeutic use. 
 
Description of Procedures 
1. If it is determined that you meet inclusion criteria and would like to be part of this study you will be asked to review 
and sign this informed consent form at time of scheduling 
 
2. You will undergo standard of care PET/CT per established protocol 
3. Following PET/CT, You will undergo an additional CT from 24 hours later to 7 days utilizing NETSPOT imaging with 
Advanced Accelerator Applications (AAA) provided dose. Neither you nor your insurance will be charged for this 
additional scan. 
4. Both images will be reviewed by the senior radiologist and the primary surgeon for concordance between images. 
Standard Update Value (SUV) will be measured for both images and recorded 
5. You will undergo clinical follow-up based on standard of care PET/CT results as per protocol 
6. True positive results will be recorded for both standard of care PET/ CT and NETSPOT images and analyzed for 
sensitivity and specificity. 
7. For patients undergoing surgical treatment, pathology results including routinely reported human papillomavirus 
(HPV) markers will be recorded and compared to NETSPOT imaging characteristics. 
Discomforts 
You will be asked to have an additional computed tomography (CT) scan. This will increase your radiation exposure by 
an additional 25%. Potential for intravenous injection complications due to a second injection include fluid infiltration, 
bleeding or bruising, venous thrombosis, and pain. As with any injected material, the risk of allergy is present; however, 
no case of anaphylaxis to 68GA-DOTATATE has been reported in the literature. A large meta-analyses on the safety of 
68Ga-DOTATATE showed that there were no serious adverse events with use. Minor side effects occurred in 3% of 
patients and included tachycardia, itching, and a drop in oxygen saturation. 
 
Alternatives 
You do not have to participate in this study. 
 
Benefits 
You may not receive any direct benefit from this study. The knowledge gained from this study may eventually benefit 


Human Research Protocol 
Only Minimal Risk Consent Form 
(With HIPAA) 
Chestnut Ridge Research Building 
886 Chestnut Ridge Road 
PO Box 6845 
Morgantown, WV 26506-6845 
P a g e | 4 
Phone: 304-293-7073 
Fax: 304-293-3098 
http://oric.research.wvu.edu 
Subject’s 
Initials 
 
Date 
 
 
 
others. 
Financial Considerations 
You will receive a $50.00 visa gift card to help pay for your return trip to WVU Medicine to receive an additional CT scan 
as requested in the study protocol. You will be paid the day of your return visit. 
 
Confidentiality 
In any publications that result from this research, neither your name nor any information from which you might be 
identified will be published without your consent. 
HIPAA 
We know that information about you and your health is private. We are dedicated to protecting the privacy of that 
information. Because of this promise, we must get your written authorization (permission) before we may use or 
disclose your protected health information or share it with others for research purposes. 
You can decide to sign or not to sign this authorization section. However, if you choose not to sign this authorization, 
you will not be able to take part in the research study. Whatever choice you make about this research study will not 
have an effect on your access to medical care. 
Persons/Organizations Providing the Information 
Patient/West Virginia University Hospitals 
 
Persons/Organizations Receiving the Information 
 
• 
The research site(s) carrying out this study. This includes UHA or UHA Affiliated, WVU, WVU Hospitals. It also 
includes each site’s research staff and medical staff 
• 
Health care providers who provide services to you as part of this research study. 
• 
Laboratories and other people and groups that look into your health information as part of this study in 
agreement with the study protocol. 
• 
The United State Department of Health and Human Services (which includes the National Institutes of Health 
(NIH), Food and Drug Administration (FDA)) and other groups that have the right to use the information as required by 
law. 
• 
The Sponsor and the people and companies that they use to oversee, manage, or conduct the research. 
• 
The members and staff of any Institutional Review Board (IRB) that oversees this research study. 
• 
West Virginia University Office of Research Integrity and Compliance and Office of Sponsored Programs. 


Human Research Protocol 
Only Minimal Risk Consent Form 
(With HIPAA) 
Chestnut Ridge Research Building 
886 Chestnut Ridge Road 
PO Box 6845 
Morgantown, WV 26506-6845 
P a g e | 5 
Phone: 304-293-7073 
Fax: 304-293-3098 
http://oric.research.wvu.edu 
Subject’s 
Initials 
 
Date 
 
 
 
The Following Information Will Be Used 
Information from your existing medical records and new information about you that is created or collected during the 
study such as: history and physicals, clinic visit notes, nursing and staff notes, laboratory results, x-rays, demographic 
data, imaging scans and study forms. 
The Information is Being Disclosed for the Following Reasons 
 
• 
Review of your data for quality assurance purposes 
• 
Publication of study results (without identifying you) 
• 
Other research purposes such as reviewing the safety or effectiveness of products or therapies; conducting 
performance reviews of products or therapies for patients; developing a better understanding of disease; improving the 
design of future clinical trials 
You May Cancel this Authorization at Any Time by Writing to the Principal Investigator 
Rusha Patel, MD 
WVU Medicine 
1 Medical Center Drive 
Morgantown, WV 26501 
If you cancel this authorization, any information that was collected already for this study cannot be withdrawn. 
Once information is disclosed, according to this authorization, the recipient may re-disclose it and then the 
information may no longer be protected by federal regulations. 
 
You have a right to see and make copies of your medical records. You will not be able to see or copy your 
records related to the study until the sponsor has completed all work related to the study. At that time you may 
ask to see the study doctor’s files related to your participation in the study and have the study doctor correct 
any information about you that is wrong. 
 
This authorization will expire at the end of the study unless you cancel it before that time. 
 
Voluntary Participation 
Participation in this study is voluntary. You are free to withdraw your consent to participate in this study at any time. 
Refusal to participate or withdrawal will not affect your future care at West Virginia University. 
In the event new information becomes available that may affect your willingness to participate in this study, this 
information will be given to you so that you can make an informed decision about whether or not to continue 
your participation. 


Human Research Protocol 
Only Minimal Risk Consent Form 
(With HIPAA) 
Chestnut Ridge Research Building 
886 Chestnut Ridge Road 
PO Box 6845 
Morgantown, WV 26506-6845 
P a g e | 6 
Phone: 304-293-7073 
Fax: 304-293-3098 
http://oric.research.wvu.edu 
Subject’s 
Initials 
 
Date 
 
 
 
 
 
You have been given the opportunity to ask questions about the research, and you have received answers 
concerning areas you did not understand. 
 
Upon signing this form, you will receive a copy. 
 
I willingly consent to participate in this research. 
 
Signatures 
Signature of Subject 
 
 
 
Printed Name 
Date 
Time 
 
 
 
 
The participant has had the opportunity to have questions addressed. The participant willingly 
agrees to be in the study. 
 
Signature of Individual Performing Consent 
 
 
 
Printed Name 
Date 
Time