Clinical trial NCT01967537
Conditions: Neuroendocrine Tumors Von Hippel-Lindau Syndrome Hippel-Lindau Disease
Keywords: NET MEN1 Von Hippel Lindau (VHL) Surgical Resection Somatostatin Receptor Status
Sponsor: National Cancer Institute (NCI)
Start date: 2013-10-18; Completion date: 2018-03-12
Enrollment: 341 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

\- Neuroendocrine tumors (NETs) are rare but have been more common over the past decade. The only treatment for NETs is surgery, but most are found when they are too advanced for surgery. Researchers are looking for the best way to find NETs earlier, so that surgery can be successful. They want to test if the study drug can be used along with imaging devices to detect NETs.

Objectives:

\- To see how well a new experimental imaging agent, 68Gallium-DOTATATE, detects unknown primary and metastatic NETs in the gastrointestinal system and pancreas.

Eligibility:

\- Adults over 10 years old with a suspected NET or family history of NET.

Design:

* Participants will be screened with a medical history and physical exam, and have a blood test.
* Participants will undergo three scans. For all of these, a substance is injected into their body, they lie on a table, and a machine takes images.
* A standard computed tomography (CT) scan of the chest, abdomen, and pelvis.
* An octreotide scintigraphy Single photon emission computed tomography (SPECT)/CT.
* A 68Gallium-DOTATATE positron emission tomography (PET)/CT. The study drug is injected into a vein, usually in the arm. Low-dose X-rays go through the body. For about 40 minutes a large, donut-shaped device takes images of the body. The entire session takes 90 to 120 minutes.
* Researchers will compare images from the three scans.
* Participants will have 1 follow-up visit each year for 5 years. At this visit, they will have a medical exam, blood taken, and a CT scan.

Detailed description:
Background:

* Neuroendocrine tumors (NETs) are rare malignancies occurring in the gastrointestinal tract, islets of the pancreas, lung, adrenal medulla and thyroid C-cells.
* Their incidence has increased over the last decade, with an incidence of 6 per 100,000 persons a year and they represent 0.46% of all malignancies.
* Most NETs are sporadic, but they can be part of familial cancer syndromes such as multiple endocrine neoplasia type 1 (MEN1), MEN2, and neurofibromatosis type 1 (NF1) or Von Hippel-Lindau (VHL) syndrome.
* Surgical resection remains the only curative treatment option for patients with NETs but 80% of patients are diagnosed with advanced (metastatic, locally inoperable, or recurrent) disease.
* The main prognostic factor in patients with NET is the extent of disease.
* The best imaging technique for detecting unknown primary and metastatic NETs has yet to be determined.
* NET cells express somatostatin receptors that can be targeted with radiolabeled 68Gallium-DOTATATE (Octreotate) for imaging purposes.
* The primary goal of this protocol is to determine the accuracy of a new somatostatin receptor targeted imaging technique, using 68Gallium-DOTATATE PET/CT to detect unknown primary and metastatic NETs.

Objectives:

-To determine the accuracy of 68Gallium-DOTATATE PET/CT scans in detecting unknown primary and metastatic gastrointestinal and pancreatic neuroendocrine tumors.

Eligibility:

* Patients with:

  * suspicion of NET on axial imaging (CT/magnetic resonance imaging (MRI)/fluorodeoxyglucose-positron emission tomography (FDG PET) and/or
  * biochemical evidence of NET (serum/urinary) based on elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), glucagon and/or
  * familial predisposition to NET in patients with multiple endocrine neoplasia type 1 (MEN1) and VHL.
* Age greater than or equal to 18 years of age.
* Patients must be willing to return to National Institutes of Health (NIH) for follow-up.

Design:

* Prospective study.
* A 68Ga-DOTATATE PET/CT scan will be done in patients with suspicious lesions, unknown primary tumor or metastatic gastrointestinal or pancreatic neuroendocrine disease found on anatomic imaging (CT/MRI) or in patients having biochemically active disease.
* Both functional and non-functional solid tumors will be included in this study. Furthermore, asymptomatic and symptomatic, sporadic and familial cases of NETs (such as Von Hippel-Lindau (VHL), MEN1) will be included.
* Demographic, clinical and pathologic data will be collected from the medical record and patient interview for each patient. Data will be stored in a computerized database.
* After their initial on-study evaluation, patients will be staged according to findings on imaging studies with respect to primary tumor site, size and metastases. Surgical resection of NET and/or medical managements will be recommended based on standard practice guidelines. In patients who undergo surgical treatment, the samples will be immediately stored until molecular analysis.
* Follow up will be done yearly for a total duration of 5 years. This includes a yearly imaging study and a biochemical and clinical evaluation, to assess tumor growth and disease progression.
* We estimate that the accrual rate will be 3-10 patients per month; the total accrual period for this study will be 10 months to 3 years.

Arms: arm 1: 68Gallium DOTATATE imaging
Interventions: intervention 1: 68Gallium DOTATATE intervention 2: Radio-guided surgery
Intervention descriptions: intervention 1: Fasting is not required prior to the imaging study. An IV line with a large bore (21 gauge or more) will be placed preferably in the antecubital vein, and, with the patient supine, around 5mCi of the 68Ga-DOTATATE will be administered intravenously, followed by incubation for approximately 60 minutes. Then the patient will be positioned in a PET/CT scanner and images from the upper thighs to the base of the skull will be obtained. In patients with tumor induced osteomalacia, images from the top of the head to the toes will be obtained. intervention 2: Using 68Gallium DOTATATE

Protocol documents:
Prot_SAP_ICF_000.pdf: 
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Clinical Investigation Monitoring Worksheet 
For Protocols using PET IND Radiopharmaceuticals 
 
 
NIH /CC/PET Department 
The Food and Drug Administration (FDA) and the NIH Intramural Research Program require that 
the Positron Emission Tomography (PET) Department, NIH Clinical Center, ensures that every 
clinical research study performed using an IND it sponsors, has an adequate monitoring plan of 
the clinical investigation. 
 
The Investigator can choose to follow their IC Guidelines/SOP to monitor the clinical 
investigation, or due to the “Low Risk” categorization of observational studies that use PET IND 
Radiopharmaceuticals, choose to conduct an annual monitoring of the clinical investigation by 
completing the following worksheet. The monitoring worksheet may be completed at the time 
of Continuing Review by the Principal Investigator or a designee (designee must be familiar with 
the study. Completed worksheet must be signed by the PI.  
 
This worksheet is designed to assist investigators to conduct basic monitoring of their clinical 
investigation and identify areas where quality improvement may be needed. The key elements 
incorporated into this monitoring worksheet are protocol compliance, patient safety, and 
quality improvement.  
 
Please complete, sign and return worksheet to the Tara Norouzi at the PET Department: 
Tara Norouzi NIH/CC/PET 
10 Center Drive, MSC1180 (Rm 1C-482) Bethesda, MD  20892   
Phone: 301-435-8505  Fax: 301-480-5695 . norouzit@cc.nih.gov 
 
Definitions 
AE 
Any untoward medical occurrence associated with the use of a drug in humans, whether or not 
considered drug related 
SAE 
A serious adverse drug experience, resulting in death, life-threatening adverse drug experience, 
hospitalization, disability or congenital abnormality 
Source Documents 
Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory 
notes, memoranda, evaluation checklists, pharmacy dispensing records, recorded data from 
automated, x-rays, subject files) 
CRFs 
Case Report Forms are printed, optical, or electronic document(s) designed to record all of the 
protocol-required information. On-site monitoring should identify data entry errors (e.g., 
discrepancies between Source Documents and CRFs) and provide assurance that there are no 
missing data in source documents or CRFs 
CAPA  
Corrective And Preventive Action  
Deviation 
Any alteration/modification to the IRB-approved protocol 
Site Signature and 
Delegation Log 
A document that contains a list of all research staff involved in the conduct of the study, 
signatures, initials, delegated tasks and effective dates 
 


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GENERAL INFORMATION 
 
Protocol Number:  
 
Rad Auth Number (if available):   
Investigational Drug(s): 
 
IND Sponsor: 
PET Department, NIH 
Protocol Title:  
 
 
 
Principal Investigator (PI):  
 
Reporting Period (covering this 
monitoring report) 
 
Date(s) Monitoring Conducted: 
 
Name of Monitoring Personnel: 
Job Title: 
Contact (Telephone): 
 
 
 
 
 
 
 
 
 
 
MONITORING CRITERIA (Choose option A or B) 
 
Option A 
         Annual Worksheet   (complete this monitoring worksheet)         
 
______________ Total No. of participating subjects in this reporting period       
 
______________ No. of subject files randomly chosen to be monitored by this worksheet  
                           (Monitoring of 10% of total No. of participating subject annually is recommended)  
STATEMENTS OF COMPLIANCE 
I understand and endorse the information in this clinical investigation monitoring worksheet.  I 
agree to notify the IND sponsor if any of the information provided in this worksheet is amended.   
                  THIS WORKSHEET MUST BE SIGNED BY THE PRINCIPAL INVESTIGATOR  
Investigator’s signature 
 
 
 
Date 
 
 
Option B 
 

Monitoring was conducted Per IC Requirements  
                         (provide IC monitoring report to IND sponsor) 
 


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NOTE: THIS WORKSHEET MUST BE SIGNED BY THE PRINCIPAL INVESTIGATOR. 
 
ESSENTIAL CLINICAL MONITORING ELEMENTS  
SUBJECT OR FILE IDENTIFICATION No. _________________ 
(This form must be completed for each subject file that is selected to be monitored) 
 
 
13 File Management                                                                                               * Response requires CAPA 
1 Is the most recent protocol version available? 
Yes    No * 
2 If yes, state the protocol version 
Version # _______________ 
3 Is a signed FDA Form 1572 and Financial Disclosure 
documentation available? 
Yes    No *
4 Is there a Site Signature and Delegation Log? 
Yes    No *
5 Is there a document that assures IRB approval was 
obtained prior to enrollment of the subjects in the 
study? 
Yes    No * 
 
14 Safety                                                                                                                  * Response requires CAPA 
6 
Were there any occurrences of AE or SAE’s? 
Yes    No  
 
(If “Yes” complete 7-9, if “No” skip 7-9)  
 
7 
Was AE/SAE Investigated and documented? 
Yes    No *                        
8 
Was AE/SAE Reported to IRB? 
Yes    No *    
9 
Was AE/SAE Reported to IND Sponsor? 
Yes    No *   
10 Was there any AE/SAE that was missed and not 
reported? 
Yes*  No 
11 Were there any deviations to the protocol? 
Yes    No  
12 If “Yes” was deviation reported the IRB and 
Sponsor? 
Yes    No * 
 
15  Consent Form                                                                                                    * Response requires CAPA 
13 Was a consent form obtained? 
Yes    No *
14 If yes, was the most current IRB approved 
consent form used? 
Yes    No *
15 If yes, what is the expiration date of the consent 
form? 
Date Consent form filled out_________ 
Exp. Date of Consent form __________ 
16 Was the consent form signed and dated by 
patient or guardian? 
Yes    No *
17 Was the subject’s signature/date on consent 
form prior to initiation of the study-specific 
procedure(s)? 
Yes    No *


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18 Was a copy of the signed consent given to 
subject?  
Yes    No *
19 If yes, is there documentation in the subject’s 
medical record that the copy was given? 
Yes    No * 
16 Subject Records (Patient Study Binder)                                                       * Response requires CAPA 
20 Are Source Documents available and reviewed? 
Yes    No *
21 If applicable, are the CRFs available and verified to 
ensure accuracy with the source documents? 
Yes    No *    N /A  
22 Was the PET Radiopharmaceutical administered 
per protocol specifications? 
Yes    No *
23 Is there a document that lists inclusion / exclusion 
criteria? 
Yes    No *
24 Did the subject enrolled meet all inclusion / 
exclusion criteria? 
Yes    No *
25 Has the subject missed any visits specified in the 
protocol? 
Yes    No 
26 If yes, were the missed visits and the reason 
documented? 
Yes    No *
 
 
 
CAPA (CORRECTIVE AND PREVENTIVE ACTION) 
List actions taken to correct deficiencies as a result of this monitoring. This is a tool for quality 
improvement. Attach additional pages if needed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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