A Comparison of NETSPOT Imaging Versus F-FDG-PET in Head and Neck Cancer Patients
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Sponsor: West Virginia University

 
 
 
 
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.