Determining the Magnitude of Change in [18F]FPIA-detectable Short Chain Fatty Acid Uptake in Metastatic Renal Cell Cancer Following Therapy
Conditions: Metastatic Renal Cell Carcinoma
Sponsor: Imperial College London

     
       
        
                                
 
 
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Determining the Magnitude of Change in [18F]FPIA-detectable Short Chain 
Fatty Acid Uptake in Metastatic Renal Cell Cancer Following Therapy 
 
Short Title: mRCC therapy response by FPIA PET/CT 
 
 
 
Sponsor: 
Imperial College London 
Funder:       
Medical Research Council  
Protocol Version :    0.9 
Protocol Date:          13May2022 
IRAS Project ID:        283224 
REC reference:  
20/WS/0150 
 
 
Protocol authorised by:  
 
 
  
Name & Role 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

     
       
        
                                
 
 
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CONTACT LIST 
 
Chief Investigator 
Dr Naveed Sarwar 
Consultant in Medical Oncology,  
Imperial College Healthcare NHS Trust 
1st Floor East Medical Oncology 
Charing Cross Hospital  
Fulham Palace Road 
London, W6 8RF 
Tel: 02033111403 
Email: naveed.sarwar1@nhs.net 
 
Co Investigators: 
 
Professor Eric Aboagye 
 
Professor of Cancer Pharmacology & Molecular Imaging,  
Imperial College London 
Commonwealth Building GN1  
Hammersmith Campus, 
Du Cane Road, London,W12 ONN 
Email: eric.aboagye@imperial.ac.uk 
 
Dr Tara Barwick 
 
Dual-accredited Radiology & Nuclear Medicine Physician 
Honorary Clinical Senior Lecturer Dept of Surgery and Cancer, Imperial College London. 
Nuclear Medicine Department,  
Imperial College NHS Trust.  
Fulham Palace Road,  
London, W6 8RF 
Email: tara.barwick@nhs.net 
Professor Andrea Rockall   
Clinical Chair of Radiology, Imperial College London and Hon Consultant Radiologist  
Imperial College Healthcare NHS Trust 
1st Floor, ICTEM building,  
Hammersmith Campus,  
Imperial College London,  
Du Cane Road,  
London, W12 ONN 
Email: a.rockall@imperial.ac.uk 

     
       
        
                                
 
 
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Dr Preetha Aravind 
Clinical Research Fellow 
Imperial College London 
Commonwealth Building GN1  
Hammersmith Campus, 
Du Cane Road, London,W12 ONN 
Email: preetha.aravind@nhs.net  
 
 
Dr Neva Patel 
Senior Nuclear Medicine and PET/CT Physicist 
Imperial College Healthcare NHS Trust 
Radiological Sciences Unit 
Fulham Palace Rd, 
London, W6 8RF 
Email: neva.patel1@nhs.net  
 
Study Co-ordination 
Comprehensive Cancer Imaging Centre  
Imperial College London 
Commonwealth Building GN1  
Hammersmith Campus, 
Du Cane Road,London,W12 0NN 
Tel: +44 (0)20 331 33720  
Email: ccic-research@imperial.ac.uk  
 
 
Clinical Queries: Clinical queries should be directed to Dr Naveed Sarwar who will direct the 
query to the appropriate person 
 

     
       
        
                                
 
 
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Sponsor: 
 
Funder: 
 
 
This protocol describes the ‘Determining the Magnitude of Change in [18F]FPIA-detectable 
SCFA Uptake in Metastatic Renal Cell Cancer Following Therapy’ and provides information 
about procedures for entering participants. Every care was taken in its drafting, but 
corrections or amendments may be necessary. These will be circulated to investigators in the 
study. Problems relating to this study should be referred, in the first instance, to the Chief 
Investigator. This study will adhere to the principles outlined in the UK Policy Framework for 
Health and Social Care Research. It will be conducted in compliance with the protocol, the 
Data Protection Act and other regulatory requirements as appropriate. 
 
Clinical Queries: Clinical queries should be directed to Dr Naveed Sarwar who will direct the 
query to the appropriate person 
 
 
 
 
 
 
Imperial College London is the main research Sponsor for this study.  
For further information regarding the sponsorship conditions, please contact the Head of 
Regulatory Compliance at:  
Joint Research Compliance Office  
Imperial College London and Imperial College Healthcare NHS Trust  
Room 215, Level 2, Medical School Building  
Norfolk Place  
London, W2 1PG  
Tel: 0207 594 9459/ 0207 594 1862 
http://www3.imperial.ac.uk/clinicalresearchgovernanceoffice  
Medical Research Council 
One Kemble Street London, WC2B 4AN 

     
       
        
                                
 
 
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Investigator Protocol Agreement Page 
 
 
• 
I confirm agreement to conduct the study in compliance with the protocol. 
• 
I acknowledge that I am responsible for overall study conduct. 
• 
I agree to personally conduct or supervise the described clinical study in accordance 
with Good Clinical Practice requirements. 
• 
I agree to ensure that all associates, colleagues and employees assisting in the conduct 
of the study are informed about their obligations.  
• 
I authorise this protocol. 
 
 
Chief Investigator Name: 
Dr. Naveed Sarwar  
 
Investigator Address: 
Consultant in Medical Oncology, Imperial College 
Healthcare NHS Trust 
1st Floor East Medical Oncology 
Charing Cross Hospital  
Fulham Palace Road 
London, W6 8RF 
Tel: 020 331 11478 
                                
 
 
Investigator Signature 
 
Date 
 
 
 
 

     
       
        
                                
 
 
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TABLE OF CONTENTS 
1    LIST OF ABBREVIATIONS and TERMS ............................................................................ 8 
2  
SYNOPSIS .................................................................................................................. 9 
3  
BACKGROUND AND RATIONALE .............................................................................. 12 
3.1 Background ...................................................................................................................... 12 
3.2   Rationale ........................................................................................................................ 13 
4  
STUDY OBJECTIVES AND ENDPOINTS ....................................................................... 13 
4.1  
Primary:..................................................................................................................... 13 
4.2 
Secondary: ................................................................................................................. 13 
4.3 
Tertiary:..................................................................................................................... 14 
5  
STUDY PLAN AND PROCEDURE ................................................................................ 14 
5.1 
Study Overview ......................................................................................................... 14 
5.2 
Study Flow Chart ........................................................................................................ 15 
6  
PARTICIPANT ENTRY ............................................................................................... 17 
6.2  
Screening ................................................................................................................... 18 
6.3  
Inclusion Criteria ........................................................................................................ 18 
6.4  
Exclusion Criteria ....................................................................................................... 19 
6.5 
ID Assignment ............................................................................................................ 19 
7 STUDY PROCEDURES .................................................................................................... 20 
7.1   Table 1 – participant procedures ..................................................................................... 20 
7.2  Screening Period .............................................................................................................. 21 
7.3 Screening Assessments ..................................................................................................... 21 
7.3.1 
Demographic Data and Medical History ......................................................................... 21 
7.3.2  WHO Performance Status .................................................................................................. 21 
Table 2: .......................................................................................................................... 22 
7.3.3 
Pregnancy Test ................................................................................................................ 22 
7.3.4 
Laboratory Evaluations.................................................................................................... 22 
7.3.5    Tumour Biopsy .................................................................................................................. 22 
7.3.6 Follow Up period ................................................................................................................. 22 
8 COMPLETION, WITHDRAWAL AND TERMINATION CRITERIA ......................................... 23 
8.1 
Completion ................................................................................................................ 23 
8.1.1 Definition of completed subject .......................................................................................... 23 
8.1.2 Definition of an evaluable subject ...................................................................................... 23 
8.1.3 Time on study ...................................................................................................................... 23 
8.2 
Rules for subject withdrawal ...................................................................................... 23 
8.3 
Rules for terminating study ........................................................................................ 24 
8.4 
End of Study .............................................................................................................. 24 
9 
RADIOTRACER AND IMAGING ................................................................................. 25 
9.1 
Radiotracer  product details ....................................................................................... 25 
9.1.1 
Supply Packaging and Labelling ....................................................................................... 25 
9.1.2   Dispensing and Accountability .......................................................................................... 25 
9.2 
Imaging Protocol ........................................................................................................ 26 
9.3  Radiation dosimetry ........................................................................................................ 26 

     
       
        
                                
 
 
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Table 3: .......................................................................................................................... 27 
9.4 Imaging Complications ..................................................................................................... 28 
10 ADVERSE EVENTS .................................................................................................... 28 
10.1  
Definitions ................................................................................................................. 28 
10.2 
Reporting of Adverse Events ...................................................................................... 29 
10.2.1 Non serious AEs ................................................................................................................. 29 
10.2.2 Serious AEs ........................................................................................................................ 29 
11  STATISTICS AND DATA ANALYSES .............................................................................. 30 
11.1 Statistical Design ............................................................................................................ 30 
11.2 
Data Analysis ............................................................................................................. 31 
12 REGULATORY, ETHICAL AND LEGAL ISSUES ................................................................. 31 
12.1 
Good Clinical Practice ................................................................................................. 31 
12.2  
Ethics Approval .......................................................................................................... 31 
12.3 
Approval of Amendments .......................................................................................... 32 
12.4  
ARSAC Approval ......................................................................................................... 32 
12.5 
Informed Consent ...................................................................................................... 32 
12.6  
Indemnity .................................................................................................................. 33 
12.7 
Sponsor ..................................................................................................................... 33 
12.8 
Funding ..................................................................................................................... 33 
12.9 
Subject Confidentiality ............................................................................................... 33 
12.10 
Material Storage and Analysis. ............................................................................... 34 
13 DATA MANAGEMENT .............................................................................................. 35 
13.1 
Data Recording and Storage ....................................................................................... 35 
13.2 
Audits and inspections ............................................................................................... 36 
13.3 
Disclosure of Data ...................................................................................................... 36 
14 STUDY MANAGEMENT ............................................................................................ 36 
15  PUBLICATION AND DISSEMINATION .......................................................................... 36 
16 REFERENCES .............................................................................................................. 37 
 
 
 
 
 
 
 
 
 
 

     
       
        
                                
 
 
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1    LIST OF ABBREVIATIONS and TERMS                                                                                                                         
 
Abbreviation Explanation 
 
AE 
 
Adverse Event 
CI 
 
Chief Investigator  
CIF 
 
Clinical Imaging Facility 
CECT  
Contrast Enhanced Computerised Tomography 
CT 
 
Computerised Tomography 
ccRCC  
Clear Cell Renal Cell Cancer  
ECOG  
Eastern Cooperative Oncology Group  
ESMO  
European Society for Medical Oncology 
[18F]FPIA 
[18F]Fluoropivalate  
[18F]-FDG 
[18F fluorodeoxyglucose 
GMP  
Good Manufacturing Practice 
HRMS   
High Resolution Mass Spectrometry  
Hb  
 
Haemoglobin 
ICH GCP 
International Conference on Harmonisation – Good Clinical Practice 
IO 
 
Immunotherapy 
irRECIST 
Immune-related response evaluation criteria in solid tumours 
LC 
 
Liquid chromatography 
mL 
 
Millilitre 
mm 
 
Millimetre 
mRCC  
Metastatic Renal Cell Cancer 
PERCIST 
Positron Emission Tomography Response Criteria in Solid Tumours 
PET 
 
Positron Emission Tomography 
PIC 
 
Participant Identification Centre 
RCC 
 
Renal Cell Cancer 
REC 
 
Research Ethics Committee 
RECIST  
Response Evaluation Criteria in Solid Tumours 
SAE 
 
Serious adverse event 
SCFA  
Short-chain Fatty Acid 
TKI 
 
Tyrosine Kinase Inhibitor 
TMB                  Tumour Mutational Burden  
 
 
 
 
 
 

     
       
        
                                
 
 
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2  SYNOPSIS 
Title 
Determining the Magnitude of Change in [18F]FPIA-detectable SCFA 
Uptake in Metastatic Renal Cell Cancer Following Therapy 
Phase type 
Explorative biomarker investigation / Phase 2 
Objectives 
Primary: 
• Determine the magnitude of change in [18F]FPIA-detectable SCFA uptake in 
mRCC following therapy. 
Secondary: 
• To determine how [18F]FPIA-detectable SCFA uptake in healthy tissue 
compares to tumour 
• To determine if changes in [18F]FPIA-detectable SCFA uptake in mRCC at 4-6  
weeks and at 12 weeks (± 4 weeks) are related to routinely measured imaging 
changes. 
Tertiary: 
• To investigate if baseline or changes in [18F]FPIA-detectable SCFA uptake in 
mRCC correlate with mutational signature. 
• To investigate if baseline or changes in [18F]FPIA-detectable SCFA uptake in 
mRCC correlate with serum and/or urine carnitine/carnitine ester signature. 
Endpoints 
Primary: 
• Quantitative longitudinal measurement of [18F]FPIA uptake in mRCC. 
Secondary: 
• Quantitative measurement of [18F]FPIA in healthy tissue including kidneys 
• Comparison of [18F]FPIA relative to baseline at 4-6 weeks and at 12 weeks (± 
4 weeks)  to changes on a patient’s routine imaging scan e.g. CT chest-abdo-
pelvis (by RECIST 1.1), Whole body FDG-PET (by PERCIST), ultrasound or MRI. 
Tertiary: 
• [18F]FPIA uptake versus Tumour Mutational Burden (TMB) on biopsy 
material.  
• [18F]FPIA uptake versus serum and urine carnitine/carnitine ester signature. 
Sample Size 
24  
In the event of  withdrawals or unevaluable data, additional patients will be 
recruited to reach a total number of 24  evaluable  subjects. 

     
       
        
                                
 
 
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Inclusion 
Criteria 
Patients with radiological and/or histological evidence of evidence of mRCC 
who are either: 
A. Treatment naïve or newly relapsed (not currently on treatment) 
or 
B. Progressing on standard of care systemic therapy  
and 
C.  that fulfil the following criteria: 
 
1. Age ≥18 
2. Target metastases size ≥ 1cm which is not in the liver.    
3. The subject has an available diagnostic tumour biopsy of the primary 
and/or metastatic lesion taken prior to the first [18F]FPIA PET/CT. 
4. WHO performance status 0 – 2. 
5. If female, the subject is either post-menopausal (>1 year), or surgically 
sterilized (has had a documented bilateral oophorectomy and/or 
documented hysterectomy, >2 years), or if of childbearing potential, 
must have a negative urine pregnancy test at initial screening and/or 
within 2 hours prior to injection of imaging agent. 
 
 6.      eGFR of ≥30 within 3 months of [18F]FPIA injection                          
7. The subject is able and willing to comply with study procedures, and a 
signed and dated informed consent is obtained. 
8. The subject is not scheduled to start cancer treatment prior to the first 
study PET/CT scan.  
Exclusion 
Criteria 
1.   Pregnant or lactating women 
2.     Evidence of significant medical condition or laboratory finding which, in 
the opinion of the Investigator, makes it undesirable for the patient to 
participate in the trial 
3.     The subject is receiving or has received chemotherapy, immunotherapy, 
biologic therapy or investigational therapy within 14 days or five half-lives 
of a drug (whichever is longer) prior to the first dose of [18F]FPIA injection.  
4. 
The subject is scheduled to have a routine nuclear medicine or contrast 
scan the same day prior to the administration of [18F]FPIA. 

     
       
        
                                
 
 
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5.     Participants with claustrophobia or who are unable to comfortably 
tolerate the scanning procedure. 
Intervention 
Subjects will receive a single I.V. bolus injection of [18F]FPIA over a period of 
about 30 seconds (for each visit).  The tracer injection will be followed by a 
saline flush.  Patients will receive a maximum 18F activity of 370 MBq. As part 
of this study the subject will have three [18F]FPIA PET/CT scans. The first will 
be before the start of cancer treatment, the second 4-6 weeks after start of 
cancer treatment, and the third about 12 weeks after start of cancer 
treatment. 
Statistical 
Methods and 
Planned 
Analysis 
The study is an Observational Non-randomised Phase 2 study to determine the 
magnitude of change in [18F]FPIA-detectable SCFA uptake in mRCC using 
[18F]FPIA PET/CT following therapy. This is the first time we are using [18F]FPIA 
in patients with mRCC, thus we do not know a priori the magnitude of uptake.  
Statistical tests will use a 0.05 significance level and will be 2-sided unless 
otherwise noted. 24 evaluable patients will be recruited for the study with the 
Upper Confidence Interval of sensitivity to detect [18F]FPIA-detectable SCFA 
uptake set to ≥ 90%.  
 
 
      
 
 
 
 
 
 
 
 
 
 
 
 

     
       
        
                                
 
 
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3  BACKGROUND AND RATIONALE  
3.1 Background  
The morphologically and genetically heterogeneous disease – Renal cell carcinoma (RCC) – is 
the most prevalent and lethal malignancy of the kidney; non clear cell RCC especially Papillary 
RCC has a worse prognosis than Clear Cell RCC (ccRCC). At the time of diagnosis, as many as a 
fifth of patients have metastatic disease (mRCC). RCC has exhibited resistance to 
chemotherapy and radiation. Despite the evolution of tyrosine kinase inhibitors (TKIs) and 
immunotherapy (IO), long-term survival rates remain poor. Importantly, there are no 
predictive biomarkers although the International Metastatic RCC Database Consortium 
(IMDC) risk score is increasingly being used to stratify patients to their systemic therapy (see 
European Society for Medical Oncology (ESMO) guidelines1). Furthermore, useful imaging 
biomarkers of response in RCC are lacking, with [18F]FDG-PET which looks at glucose 
metabolism, and 124I-cG250 -PET which targets carbonic anhydrase IX in VHL mutated RCC 
subtypes such as ccRCC, being ones that have been extensively explored2. Notably, response 
in bone metastases are notoriously difficult to assess. 
 We have developed a new tracer, 18F-fluoropivalate ([18F]FPIA) that images short chain fatty 
acid (SCFA) uptake in tumours, a key component of fatty acid oxidation3,4. Like its non-
radioactive analogue5, [18F]FPIA is converted to FPIA-carnitine upon injection likely in the 
liver4 and is hypothesised to be transported via the blood to the tumour where it 
accumulates3,4. In collaboration with Invicro, we have conducted GMP manufacturing and 
first-in-human evaluation4. We are currently conducting studies in brain tumours due to the 
low background of this radiotracer in healthy brain compared to brain tumours, unlike FDG. 
Here we propose to study the [18F]FPIA-detectable tumour SCFA uptake in RCC and the effect 
of therapy on the signal. There is paucity of data on SCFA uptake, carnitine metabolism and 
related transporter activity in RCC, but there are strong suggestions that this may be a highly 
relevant biology of RCC. By extracting surgically removed normal kidney, ccRCC and urine 
followed by Liquid chromatography- High Resolution Mass Spectrometry (LC-HRMS), Niziol J 
and 
co-workers 
recently 
reported 
that 
SC-carnitine 
metabolites 
including 
hydroxybutyrylcarnitine and propanoylcarnitine, as well as carnitine were in much higher 
concentrations in RCC compared to paired normal tissues; and in urine of cancer patients 
compared to healthy controls6. This may be due in part to import of these metabolites from 
systemic circulation into tumour (and renal elimination) rather than increased synthesis 
within tumours, since enzymes for synthesis in tumour are downregulated in RCC7. 
Furthermore, effective treatment that alters the metabolic capacity of RCC should decrease 
import of SCFA, hence [18F]FPIA uptake. The main therapeutic options for RCC patients are 
TKIs, including Sunitinib, Axitinib, Tivozanib, Cabozantanib and Pazopanib, and more recently 
immunotherapy, including Pembrolizumab, Avelumab, Ipilimumab and Nivolumab, which can 
present with pseudo progression/pseudo response phenotypes due to changes in vascular 
physiology/perfusion or immune cell infiltration. Patients receiving these therapies as part of 
their routine care, who are being monitored by standard Response evaluation criteria in solid 

     
       
        
                                
 
 
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tumours/ 
Immune-related Response 
evaluation 
criteria 
in 
solid 
tumours 
(RECIST/PERCIST/irRECIST) will be studied. 
3.2   Rationale 
Hypothesis: Import of [18F]FPIA-detectable SCFA into tumours is high and decreases with 
effective treatment. 
Aim: To investigate longitudinal changes in [18F]FPIA uptake at baseline, and at 4-6 weeks (1-
2 cycles) and 12 weeks (± 4 weeks); (routine CECT evaluation timepoints) following treatment 
initiation in patients using TKIs, chemotherapy, IO, or combinations of these. 
 
4  STUDY OBJECTIVES AND ENDPOINTS  
 
4.1  
Primary:   
Primary Objective 
Primary Endpoint 
Determine the magnitude of change in 
[18F]FPIA-detectable SCFA uptake in mRCC 
following therapy. 
Quantitative 
longitudinal 
measurement of [18F]FPIA uptake in 
mRCC. 
 
4.2 
Secondary: 
 
Secondary Objectives 
Secondary Endpoint 
To determine how [18F]FPIA-detectable SCFA 
uptake in healthy tissue compares to tumour. 
Quantitative measurement of FPIA in 
healthy tissue including kidneys. 
To determine if changes in [18F]FPIA-
detectable SCFA uptake in mRCC at 4-6 weeks 
and at 12 weeks (± 4 weeks) are related to 
routinely measured imaging changes. 
 Comparison of [18F]FPIA relative to 
baseline at 4-6 weeks and at 12 weeks (± 
4 weeks) to changes on a patient’s 
routine imaging scan e.g. CT chest-abdo-
pelvis, Whole body FDG-PET, ultrasound 
or MRI (RECIST 1.1 or irRECIST or 
PERCIST. 
 
 
 

     
       
        
                                
 
 
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4.3 
Tertiary: 
Tertiary Objective 
Tertiary Endpoint 
To investigate if baseline or changes in 
[18F]FPIA-detectable SCFA uptake in mRCC 
correlate with mutational signature. 
[18F]FPIA 
uptake 
versus 
Tumour 
Mutational Burden (TMB) on biopsy 
material. 
To investigate if baseline or changes in 
[18F]FPIA-detectable SCFA uptake in mRCC 
correlate 
with 
serum 
or 
urine 
carnitine/carnitine ester signature. 
[18F]FPIA uptake versus serum or urine 
carnitine/carnitine ester signature. 
 
5  STUDY PLAN AND PROCEDURE 
 
5.1 
Study Overview 
24 evaluable patients (all IMDC risk groups; metastatic ccRCC or other subtypes) with 
radiological and/or histological evidence of mRCC and due to receive physician choice of 
systemic therapy will be enrolled.  The patients invited to participate in the study will provide 
written informed consent, but will only undergo [18F]FPIA PET/CT imaging once they have 
satisfied the inclusion and exclusion criteria. Once these have been satisfied, eligible patients 
will proceed to [18F]FPIA PET/CT. Patients will have three imaging visits.  Data will be 
considered complete when patients have all three analysable scans. In the event of dropout, 
additional subjects will be recruited to reach a total number of 24 evaluable  subjects.  
On each day of imaging the patients will have a blood test and a urine sample collected to 
measure concentrations of carnitine. For each scan, a single dose of [18F]FPIA (maximum, 370 
MBq) IV will be administered to the participant. The participant will then rest in a quiet place 
for an uptake period & undergo whole body PET/CT scanning from 60 min (vertex to knees). 
Archival tumour biopsies (primary or metastatic lesion), taken prior to the 1st [18F]FPIA PET/CT 
scan, will be retrieved for analysis where possible.  
 
 
 
 

     
       
        
                                
 
 
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All patients will have 3 [18F]FPIA PET/CT scan visits on different days: 
Scan 1: Baseline scan to be conducted prior to initiating standard of care therapy. 
 
Scan2:  Early post-treatment scan to be conducted at 4-6 weeks after initiating 
therapy. 
 
Scan3: Late post-treatment scan to be conducted at 12 weeks (± 4 weeks) after 
initiating therapy. 
 
 
Drug therapy pre study: Patients will have been treated as per standard of care, which may 
have included TKIs, chemotherapy, IO or combinations of these. 1st line and 2nd line  patients 
can be included in the study after washout period of 14 days or 5 half-lives of drug (whichever 
is longer) providing they fit all inclusion and exclusion criteria.  
Drug therapy on study: Patients will be treated as per standard of care, which may include 
TKIs, chemotherapy, IO and combinations of these.  
 
 
 
5.2 
Study Flow Chart 
                                                                       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Visit 
Obtain informed consent and 
confirm eligibility 
Scanning Visits 
[18F]FPIA PET/CT scans 
• 
Baseline 
• 
Early post treatment (4-6 wk) 
• 
Late post treatment (12 wk; ± 4 
weeks) 
• 
Retrieve archival biopsy 
STUDY PARTICIPATION COMPLETE 
At  
Imperial College 
Healthcare NHS Trust  
Performed at either an Imperial College 
Healthcare NHS Trust or Imperial College London 
Facility 
Participant 
Identification 
Centre (PIC) 
Referral 
Visits may be combined 

     
       
        
                                
 
 
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DRAFT Protocol version 0.8  DATE TBC                                                                                                 17 
 
6  PARTICIPANT ENTRY 
 
A target of 24 evaluable subjects will be recruited.  
In the event of withdrawals or non-evaluable data before or after dosing, additional subjects 
will be recruited to reach a total number of 24 evaluable  subjects. Evaluable data from 
patients who drop out will be used whenever possible. 
 
6.1  
Identification and recruitment of subjects 
Potentially eligible patients will be identified from the Imperial oncology multidisciplinary 
team meeting and from outpatient clinics by a member of the clinical and research team. The 
treating clinician will discuss the study with the patient at their clinic appointment and a 
patient information sheet explaining the study will be given to them or agreed to email or post 
to them either by the clinician or by a member of the clinical research team.  Patients will be 
given a minimum of 24 hours to consider participation in the study. After this time, they will 
be contacted by a member of the research team to discuss the study in more detail. Written 
and dated informed consent will be obtained prior to any protocol-specific procedures being 
performed. Patients will then be invited to attend a screening visit. The screening visit may be 
on the same day as the baseline scan. 
 
Figure 2. Recruitment pathway 
 
 
 
 
 
 
 
 
 
 
Patient 
declines 
trial
Patient 
enters trial
Proceed to 
screening 
visit for 
informed 
consent
Patient 
agrees to 
enter study
Patient 
contacted by 
study team
Patient 
approached 
at outpatient 
appointment 
and PIS 
provided
Patient 
identified at 
MDT/Clinic

     
       
        
                               
 
 
DRAFT Protocol version 0.8  DATE TBC                                                                                                 18 
 
6.2  
Screening 
Each patient will undergo screening assessments to confirm eligibility. Evaluations of the 
tumour and other clinical data obtained as standard of care prior to consent may be used for 
the study, provided they comply with the protocol specified timelines. Written informed 
consent will be obtained before the patient undergoes any study specific procedures.  
Each potential patient will be assigned a unique identifier number for use during the trial. A 
complete record of all patients who enter screening for the study, as well as those who go on 
to be enrolled must be maintained at each site.  
Eligible patients who take part in the study must meet all of the listed inclusion criteria and 
none of the exclusion criteria. 
 
6.3  
Inclusion Criteria 
 
Patients who meet all of the following inclusion criteria will be considered eligible for this 
study: 
Patients with radiological and/or histological evidence of evidence of mRCC who are either: 
A. Treatment naïve or newly relapsed (not currently on treatment) 
or 
B. Progressing on standard of care systemic therapy 
and 
C. That fulfil the following criteria: 
 
1. Age ≥18 
 
2. Target metastases size ≥ 1cm which is not in liver.    
3. The subject has an available diagnostic tumour  biopsy of the primary and/or metastatic 
lesion taken prior to  the first [18F]FPIA PET/CT. 
4. WHO performance status 0 – 2. 
5. If female, the subject is either post-menopausal (>1 year), or surgically sterilized (has had 
a documented bilateral oophorectomy and/or documented hysterectomy, >2 years), or 

     
       
        
                               
 
 
DRAFT Protocol version 0.8  DATE TBC                                                                                                 19 
 
if of childbearing potential, must have a negative urine pregnancy test at initial screening 
and/or within 2 hours prior to injection of imaging agent. 
 
6. eGFR of ≥30 within 3 months of [18F]FPIA injection  
 
7. The subject is able and willing to comply with study procedures, and a signed and dated 
informed consent is obtained. 
8. The subject is not scheduled to start cancer treatment prior to the first study PET/CT 
scan.  
 
 
6.4  
Exclusion Criteria 
Patients who meet any of the following exclusion criteria will not be considered eligible for 
this study: 
1.    Pregnant or lactating women 
2.     Evidence of significant medical condition or laboratory finding which, in the opinion of the 
Investigator, makes it undesirable for the patient to participate in the trial 
3.     The subject is receiving  or has received chemotherapy, immunotherapy, biologic therapy 
or investigational therapy within 14 days or five half-lives of a drug (whichever is longer) 
prior to the first dose of [18F]FPIA injection.  
4.     The subject is scheduled to have a nuclear medicine or contrast scan within 24 hours of 
the administration of [18F]FPIA.  
5.     Participants with claustrophobia or who are unable to comfortably tolerate the scanning  
procedure. 
 
6.5 
ID Assignment  
Subject numbers will be assigned in successive order of inclusion.  
 
 

     
       
        
                                
 
 
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7 STUDY PROCEDURES 
7.1   Table 1 – participant procedures 
 
 
-- 28 to 0 
days 
Scan 1 (Baseline pre-treatment) 
Scan 2  (4-6 weeks post treatment) 
Scan 3 (12 weeks  post treatment; +/- 4 weeks) 
 
Screening  
Pre-
PET/CT  
120mins 
Tracer 
Dose 
0 mins 
Low 
Dose 
CT 
Whole-
body PET 
sweep6 
60 min 
Post scan 
24 hrs 
Pre-
PET/CT  
120mins 
Tracer 
Dose 
0 mins 
Low 
Dose 
CT 
Whole-
body PET 
sweep6 
60 min 
Post scan 
24 hrs 
Informed Consent 
• 
 
 
 
 
 
 
 
 
 
 
Entry Criteria 
• 
 
 
 
 
 
 
 
 
 
 
Medical History 
• 
 
 
 
 
 
 
 
 
 
 
Treatment History1 
• 
• 
 
 
 
 
• 
 
 
 
 
Height2 / Weight 
 
• 
 
 
 
 
• 
 
 
 
 
Pregnancy Test3 
 
• 
 
 
 
 
• 
 
 
 
 
WHO Performance 
status 
• 
 
 
 
 
 
 
 
 
 
 
Renal function 
eGFR4 
• 
 
 
 
 
 
 
 
 
 
 
Carnitine (blood)5 
 
• 
 
 
 
 
• 
 
 
 
 
Carnitine (urine)6 
 
• 
 
 
 
 
• 
 
 
 
 
[18F]FPIA injection 
 
 
• 
 
 
 
 
• 
 
 
 
PET scanning7 
 
 
 
 
• 
 
 
 
 
• 
 
Adverse events8 
 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Tumour Biopsy9 
 
 
 
 
 
 
 
 
 
 
 

     
       
        
                                
 
 
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7.2  Screening Period 
Subjects will be screened up to 28 days before tracer administration to confirm eligibility.   
Signed and dated informed consent must be obtained from all subjects prior to any 
protocol specific procedures being performed. 
 
7.3 Screening Assessments 
7.3.1 Demographic Data and Medical History 
Demographic data and other characteristics will be recorded and will include date of birth, 
height, weight. 
A standard medical history will be obtained including details of previous cancer  
treatment, surgical history and tumour characteristics. 
7.3.2  WHO Performance Status 
Performance status will be assessed at the scheduled time points indicated in Table 1 
according to WHO criteria as follows: 
 
1. Cancer treatment history.  
2. Repeat Height measurement not required at scans 2 and 3. 
3. In women of child bearing potential. On scan day, must be carried out within 2 hours prior to 
injection of imaging agent. 
4. Review of  standard of care eGFR bloods taken within 3 months of [18F]FPIA injection or new 
sample (≤6mls). 
5. Approximately 15 mls 
6. Approximately 20mls 
7. PET/CT scanning protocol is the same for all scans. Includes low dose CT for anatomical 
localisation and attenuation correction of the PET data. 
8. Adverse events related will be collected for each 24 hour period post each PET/CT scan. 
9. A diagnostic tissue biopsy of the primary and/ or metastatic lesion obtained prior to the 1st scan 
will be retrieved for analysis at any time during study participation.   

     
       
        
                                
 
 
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Table 2:  
 
0 
Fully active, able to carry on all pre‐disease activities without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature. For example, light housework, office work 
2 
Ambulatory and capable of all self‐care but unable to carry out any work activities. Up 
and about more than 50% of waking hours 
3 
Capable of only limited self‐care, confined to bed or chair 50% or more of waking hours 
4 
Completely disabled. Cannot carry on any self‐care. Totally confined to bed or chair 
5 
Death 
 
 
7.3.3 Pregnancy Test 
A urine pregnancy test will be performed within 2 hours prior to injection of the imaging 
agent in women of childbearing potential.   
7.3.4 Laboratory Evaluations 
Blood samples for renal function may have been taken as standard of care in this patient 
population. Results of blood tests taken within 3 months of the scan can be used for study 
purposes. A new blood sample will be taken if a result is not available (aproximately 6 
mls). 
 
New blood and urine samples will be taken for carnitine testing prior to each PET/CT 
scan. 
7.3.5    Tumour Biopsy 
A diagnostic tissue biopsy of the primary and/ or metastatic lesion obtained prior to the 
1st scan will be retrieved for analysis of TMB. 
7.3.6 Follow Up period 
There is no study specific FU following the final research PET/CT. AEs will be reportable 
for up to 24 hours post each scan. The patients will be assessed and followed up in all 
routine clinical procedures as per local policy by the treating clinician.  
 
 

     
       
        
                                
 
 
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8 COMPLETION, WITHDRAWAL AND TERMINATION CRITERIA 
 
8.1 Completion 
8.1.1 Definition of completed subject  
A completed subject is one who has completed all imaging sequences of the combined 
[18F]FPIA PET/CT protocol.  
8.1.2 Definition of an evaluable subject 
An evaluable subject is one who has completed study and where the images from the 
[18F]FPIA PET/CT are of sufficient quality for analysis. 
In the event of withdrawals or non-evaluable data before or after dosing, additional 
subjects will be recruited to reach a total number of 24 evaluable subjects. 
8.1.3 Time on study 
The last study related visit for a subject would be the final research PET/CT  scan. There 
are no follow up patient visits unless follow up for resolution of Adverse Events is 
required. 
Depending on the screening period taken in relation to the scan day and approximating a 
treatment start within 4 weeks of the baseline scan,  a subject can be on study between 
12 and 21 weeks plus a 24 hour post scan reportable Adverse Event period.  
8.2 
Rules for subject withdrawal 
There are no formal withdrawal criteria for this study.  During the conduct of the study, 
the study team will review the safety data for trends and signals that would indicate the 
need for withdrawal of a subject.  
In accordance with the Declaration of Helsinki, each subject is free to withdraw from the 
study at any time.  Investigator(s) also have the right to withdraw subjects from the study 
in the event of illness, AEs, or other reasons concerning the health or well-being of the 
subject, or in the case of lack of co-operation. Should a subject decide to withdraw after 
administration of the tracer, or should the investigator decide to withdraw the subject, 
all efforts will be made to complete and report the observations up to the time of 
withdrawal as thoroughly as possible.  A complete final evaluation at the time of the 

     
       
        
                                
 
 
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subject’s withdrawal will be made and an explanation given of why the subject is 
withdrawing or being withdrawn from the study.   
Subjects who discontinue standard of care treatment before scan visit 2 will not proceed 
to scan 2 or scan 3. 
Subjects who discontinue standard of care treatment between scan visit 2 and scan visit 
3 will be reviewed by the investigator with regard to proceeding to scan visit 3 depending 
on proximity of treatment cessation to final scan window. 
The reason for non-completion and the date and time of the last contact with the subject 
must be noted in the research documentation. If the reason for withdrawal is a clinical AE 
or an abnormal laboratory result, monitoring will continue until the outcome is evident.  
The specific event or test result(s) must be recorded in the research documentation.  
8.3 
Rules for terminating study 
The sponsor reserves the right to terminate the study at any time. Prior to dosing of the 
first subject, the study may be terminated by the sponsor and the investigator without 
consultation with the Administration of Radioactive Substances Advisory Committee 
(ARSAC) holder and Ethics Committee. The ARSAC holder, Ethics Committee and Health 
Research Authority (HRA), must be promptly notified that the study will no longer be 
taking place and provided with a detailed written explanation.  Once dosing with 
radiopharmaceutical has begun, the study may only be terminated if a careful review of 
the overall risk benefit analysis demonstrates that the assumptions have changed and 
that the overall balance is no longer acceptable. The investigators will temporarily halt 
the study if there has been a SAE which has been judged to be related to the study dosing. 
In these circumstances, termination can only take place with the agreement of the ARSAC 
holder and the Ethics Committee. 
If it becomes necessary to consider termination of the study after dosing has begun, 
dosing may be suspended pending discussion between the sponsor, the investigator, the 
ARSAC holder and the Ethics Committee.  Dosing may always be immediately suspended 
for safety reasons.  
8.4 
End of Study 
The end of the study is defined as the last visit of the last patient undergoing the study. 
 

     
       
        
                                
 
 
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9 RADIOTRACER AND IMAGING 
 
9.1 
Radiotracer  product details  
[18F]FPIA is a radiotracer which is used in PET imaging. All PET imaging and therefore all 
handling of [18F]FPIA will occur at either an Imperial College Healthcare NHS Trust or 
Imperial College London Facility. Recruitment sites will not handle [18F]FPIA. 
9.1.1 Supply Packaging and Labelling 
Due to the short half‐life of [18F]FPIA, supply will be on a per‐patient basis. 
[18F]FPIA will be packaged, labelled and distributed by an appropriate courier to sites by 
the University College London GMP facility. 
Labels will be prepared in accordance with Good Manufacturing Practice Annexe 13 
requirements and local regulatory guidelines. 
9.1.2   Dispensing and Accountability 
[18F]FPIA will be dispensed as per local practice at the Imperial College London or Imperial 
College Healthcare NHS Trust Facility and only by staff authorised to do so by the principal 
investigator.  
[18F] activity will be measured using a calibrator according to the working instructions at 
the site. Volumes will be adjusted to avoid counter saturation. 
Unused [18F]FPIA will be reconciled, accounted for and disposed of by the Imperial College 
London or Imperial College Healthcare NHS Trust Facilities according to local guidelines.  
Radiotracer accountability records will be maintained throughout the course of the study 
and filed with delivery documentation.   
The investigators are responsible for ensuring that deliveries of the tracer and study 
material are correctly received, recorded, handled and stored safely and properly, in 
accordance with regulatory guidelines (ICH-GCP and Good Manufacturing Practice 
(GMP) and used in accordance with this protocol. 
 
 

     
       
        
                                
 
 
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9.2 
Imaging Protocol 
 [18F]FPIA PET/CT imaging will occur at an Imperial College Healthcare NHS Trust or 
Imperial College London Facility 
Patients taking part in this study will have whole body  [18F]FPIA PET/CT imaging on each  
of 3 scan visits (baseline/4-6 weeks post therapy/ 12 weeks post therapy (± 4 weeks)). 
Patients will receive a dose of [18F]FPIA on each of the 3 scan days.  
• Patients will attend the site imaging facility on the scan day. 
• Pre-scan assessments will be carried out as per Table 1. 
• A small cannula will be inserted into a vein in an arm and a blood sample taken for 
carnitine testing. 
• At 60 minutes prior to the planned PET scan start time, the patient will be injected 
with a maximum administered activity 370 MBq [18F]FPIA in a suitable upper limb 
vein. The administration will be followed by a saline flush. 
• After an uptake period of approximately 50 minutes, the patient will be asked to 
void urine and made comfortable on the scanner bed. 
• At approximately 55minutes after injection of [18F]FPIA, the patient will undergo 
a low-dose whole body CT scan, (skull vertex to knees) for attenuation correction 
purposes and to facilitate accurate anatomical localization. 
• They will undergo whole-body (skull vertex to knees) PET imaging at 60 minutes. 
For follow up scans the timing will be as for visit 1 +/- 5 minutes. 
• The cannula will be removed at the end of the scan 
• The actual dose of [18F]FPIA administered will be recorded in the study notes. 
• AEs will be reportable for up to 24hours after the scan. 
• The imaging acquisition will be the same for all [18F]FPIA PET/CT imaging sessions. 
 
 
 
 
 
 
 
 
9.3  Radiation dosimetry  

     
       
        
                                
 
 
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27 
 
The total ionising radiation exposure will be from both PET and CT scans combined. 
Participants will have three [18F]FPIA PET/CT scan visits.  
 
Table 3: 
Tracer 
[18F]FPIA 
low-dose CT for attenuation  
Whole Body 
(skull vertex to knees) 
Maximum injected dose per 
scan 
370MBq 
 
Effective dose (mSv/MBq)  
0.0154 mSv/MBq  
 
Effective dose (mSv)/scan  
5.7 
6.00 
Total Research Protocol Dose 
(TRPD)  
(3 PET/CT scan visits) 
= 35.1 mSv 
 
Each patient that participates in this study will have 3 PET/CT scans in addition to their 
standard of care. 
The imaging protocol and associated dosimetry is as per Table 3. 
Following an uptake period, the participant will undergo a low dose CT for attenuation 
correction of PET data (with a dose constraint of 6.0 mSv and image acquisition lasting 
approximately 30 minutes in total). The radiation dose from 370MBq [18F]FPIA will be 5.7 
mSv (Dubash et al. 2020). The maximum additional radiation dose from one [18F]FPIA 
PET/CT will be 11.7 mSv.  
The maximum Total Research Protocol Dose (TRPD) from this study is therefore 35.1 mSv.  
The radiation dose required by the study is additional to routine clinical care.  
For comparison, the average annual natural background radiation dose in the UK is 2.3 
mSv. The TRPD incurred in this study can be compared to approximately 15.3 years of 
naturally occurring background radiation exposure. 

     
       
        
                                
 
 
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The risk of developing cancer as a consequence of taking part in this study is estimated as  
0.18% (or 1 in 570). For comparison, the natural lifetime cancer incidence in the general 
population is about 50% (1 in 2).  
The radioactive fluorine in the tracer decays by half every 109.7 minutes  which means 
that little will remain in the body by the time the patient leaves the scanning centre.  
9.4 Imaging Complications  
There are no immediate complications anticipated from the PET/CT scan except for  
potential mild bruising at the site of insertion of the peripheral cannula which should 
resolve within a few days. Rarely,  the participant may feel dizzy after the scan due to lying 
flat, but this is normally short lived  
Scans will be stopped at any time during the procedure if the subject is unable to tolerate 
it. 
 
10 ADVERSE EVENTS 
 
10.1  Definitions  
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study 
subject. 
 Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or 
effect that:  
• Results in death; 
• Is life‐threatening*; 
•Requires 
hospitalisation 
or 
prolongation 
of 
existing 
inpatient’s    
hospitalisation**; 
• Results in persistent or significant disability or incapacity; 
• Is a congenital abnormality or birth defect; 
* “Life‐threatening” in the definition of “serious” refers to an event in which the patient 
was 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. 

     
       
        
                                
 
 
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** “Hospitalisation” means any unexpected admission to a hospital department. It does 
not usually apply to scheduled admissions that were planned before study inclusion or 
visits to casualty (without admission). 
Medical judgement should be exercised in deciding whether an adverse event/reaction is 
serious in other situations. Important adverse events/reactions that are not immediately 
life‐threatening, or do not result in death or hospitalisation but may jeopardise a patient, 
or may require intervention to prevent one of the other outcomes listed in the definition 
above should also be considered serious. 
 
10.2 
Reporting of Adverse Events 
10.2.1 Non serious AEs 
AEs will be collected from the start of each scan visit  to  up to 24 hours after each PET/CT 
scan.  
Any AEs which remain unresolved at the patient’s last visit in the study should be followed 
up by the Investigator for as long as medically indicated. 
Depending on the nature of the event the reporting procedures below should be 
followed. Any questions concerning adverse event reporting should be directed to the 
Chief Investigator in the first instance 
10.2.2 Serious AEs 
An SAE form should be sent to the Chief Investigator with 24 hours. However, relapse, 
death and/or hospitalisations for elective treatment of a pre-existing condition do not 
need reporting as SAEs.  
 
All SAEs will be reviewed by the Chief Investigator or a designated medically qualified 
representative to confirm expectedness and causality. 
 
All SAEs should be reported to the relevant REC where in the opinion of the Chief 
Investigator, the event was:  
 
• ‘Related’, i.e. resulted from the administration of any of the research procedures; and  
• ‘Unexpected’, i.e. an event that is not listed in the protocol as an expected occurrence  
 

     
       
        
                                
 
 
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Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies. 
The Chief Investigator must also notify the Sponsor of all SAEs.  
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
 
Please send SAE forms to the Sponsor and CI to the below email addresses: 
 
 
 
11  STATISTICS AND DATA ANALYSES 
 
11.1 Statistical Design  
The study is an Observational Non-randomised Phase 2 study to determine the magnitude 
of change in [18F]FPIA-detectable SCFA uptake in mRCC using [18F]FPIA PET/CT following 
therapy. This is the first time we are using [18F]FPIA in patients with mRCC, thus we do not 
know a priori the magnitude of uptake.  Statistical tests will use a 0.05 significance level 
and will be 2-sided unless otherwise noted. 24 evaluable patients will be recruited for the 
study with the Upper Confidence Interval of sensitivity to detect [18F]FPIA-detectable 
SCFA uptake set to ≥ 90%.  
 
 
 
 
 
Contact details for reporting SAEs are as follows: 
 
 jrco@imperial.ac.uk (Sponsor E-mail) 
naveed.sarwar1@nhs.net (CI E-mail) 
Tel: 020 331 11403 (CI telephone) 
Please send SAE forms to the Sponsor and CI on the above email addresses: 
 (Mon to Fri 09.00 -17.00) 

     
       
        
                                
 
 
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31 
 
11.2 
Data Analysis 
The clinical data will be entered and stored in an appropriate database. An early stage 
review  of tracer uptake after 5 cases will be carried out. A final analysis will be conducted 
at the end of the study.  
The data analysis will consist of completed cases, i.e. all patients who completed the 
[18F]FPIA scans and 12 weeks (± 4 weeks) of therapy. This is because the primary endpoint 
of change in uptake of [18F]FPIA from baseline is measured based on the PET/CT scans 
pre- and post- therapy.  
Analysis of the imaging data will be quantified using SUV. The whole body scans will 
provide response information (change in SUV) on non-target and target lesions combined. 
Regions of interest (ROIs) corresponding to tumour and healthy tissue will be drawn on 
PET images and used to derive semi-quantitative uptake parameters. These may include 
SUVmean (mean of standardized uptake values (SUV) within an ROI) normalised to body 
weight (bw), SUVmax and SUVpeak; tumour to background ratio. 
The analysis will be reviewed by an experienced investigator/ radiologist/ statistician.  
The following associations will be determined: between PET and biological measures 
• The relationship between PET and cell proliferation determined by histology. 
• The relationship between PET and biological drivers of fatty acid metabolism 
determined by histology. 
 
12 REGULATORY, ETHICAL AND LEGAL ISSUES  
 
12.1 
Good Clinical Practice 
The study will be conducted in accordance with the guidelines laid down by the 
International Conference on Harmonisation for Good Clinical Practice (ICH GCP E6 
guidelines). 
12.2  Ethics Approval 
The Study Coordination Centre has obtained approval from the West of Scotland 
Research Ethics Committee (REC) 5 and Health Regulator Authority (HRA). The study must 
also receive confirmation of capacity and capability from each participating NHS Trust 
before accepting participants into the study or any research activity is carried out. The 

     
       
        
                                
 
 
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32 
 
study will be conducted in accordance with the recommendations for physicians involved 
in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 
1964 and later revisions. 
 
12.3 
Approval of Amendments 
Proposed amendments to the protocol and aforementioned documents must be 
submitted to the HRA/REC for approval as instructed by the Sponsor. Amendments 
requiring HRA/REC approval may be implemented only after a copy of the all necessary 
approval letters have been obtained. Imperial College London Sponsor approval is 
required before any amendments are made with the exception of urgent safety measures. 
Amendments that are intended to eliminate an apparent immediate hazard to subjects 
may be implemented prior to receiving Sponsor or REC approval. However, in this case, 
approval must be obtained as soon as possible after implementation. 
12.4  ARSAC Approval 
Employer and Practitioner Administration of Radioactive Substances Advisory Committee (ARSAC) 
certificates will be required for the specified tracer and indication, and both the employer and 
practitioner must be authorised to use this tracer for research purposes. 
 
The Chief Investigator will ensure that the procedures are compliant with the Ionising 
Radiation (Medical Exposure) Regulations, and appropriate review by a Medical Physics 
Expert and Clinical Radiation Expert has been undertaken. 
 
12.5 
Informed Consent 
The Chief Investigator will: 
• Ensure that the right of the participant to refuse to participate without giving 
reasons is respected. 
 
• Ensure that each patient is given full and adequate oral and written information 
about the study including the background, purpose and risks/benefits of 
participation and the risk associated with the radiation exposure from the PET 
tracer. 
• Ensure that each patient is notified that they are free to withdraw from the study 
at any time without giving reasons and without prejudicing further treatment. 

     
       
        
                                
 
 
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33 
 
• Ensure that each patient is given the opportunity to ask questions and allowed 
sufficient time to read and understand the information sheet 
• Ensure each patient provides signed, dated informed consent before undergoing 
any study specific procedure 
• Ensure the original copy of the signed, dated Informed Consent Form is stored 
in the Investigator site file and a copy is also filed in the medical records 
• Ensure that each patient receives a copy of the signed, dated Informed Consent 
Form 
 
12.6  Indemnity 
Imperial College London holds negligent harm and non- negligent harm insurance policies, 
which apply to this study. 
12.7 
Sponsor 
Imperial College London will act as the main Sponsor for this study. Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.  
12.8 
Funding 
This study is funded by the Medical Research Council (MRC). 
Patient travel expenses to attend study visits will be reimbursed where necessary. 
Patients will not be paid for taking part in the study. 
12.9 
Subject Confidentiality 
Imperial College London and Imperial College NHS Trust data protection policies will be 
followed. Subjects personal data will be available only to clinical and research members 
directly involved in the study conduct. The Chief Investigator will preserve the 
confidentiality of participants taking part in the study and is registered under the Data 
Protection Act. 
Participants will be allocated a unique study identifier code which will be known to the 
study research team and staff. The study identifier code will be used to pseudonymise 
samples, results, datasets and scans which would be held electronically on Imperial 
College London computers . 

     
       
        
                                
 
 
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34 
 
Subjects’ identification data will be required for the recruitment, screening and 
registration processes. On study documents submitted to the Sponsor, patients will be 
identified by a trial ID number only. Documents that are not submitted to the Sponsor 
(e.g. signed informed consent form) will be kept in a strictly confidential file by the 
investigator. 
The Chief  Investigator shall permit direct access to patients’ records and source 
document for the purposes of monitoring, auditing, or inspection by the Sponsor, 
authorised representatives of the Sponsor, Regulatory Authorities and REC. 
The imaging facility staff at Imperial College Healthcare NHS Trust and Imperial College 
London will have access to limited participants' personal data for registration, IRMER, 
safety and governance purposes but may need to view the participant's medical records 
in the event of any study adverse events or emergencies on the scan day.  
The subject’s GP will be informed of their participation in the study.  
The taxi company will be given the name address & contact number of the subject by 
email, e booking or telephone. 
12.10 Material Storage and Analysis. 
Blood samples for renal function will be analysed by Imperial College Healthcare NHS 
Pathology department and  identifiable results reported on a secure web-based results 
reporting system under the Imperial NHS Trust data protection policy, only accessible by 
NHS contracted staff.  
Blood and urine samples for carnitine will be pseudonymised, processed as required and 
stored at Imperial College London. They will be analysed at Imperial College London and  
at an external laboratory and will not be identifiable to laboratory personnel.  
Urine samples for pregnancy testing will be pseudonymised and tested immediately by 
research staff.   
All above samples will be disposed of after testing according to local policies. 
The tumour specimens will be accessed from the Tissue Bank and stored as per Human 
Tissue Authority (HTA) regulations. All samples will be pseudonymised with the link only 
being known to the research team. Approval will be sought for tumour tissue sample use 
according to local guidelines. Tissue will be analysed within Imperial College London. 
Diagnostic archived tumour samples will be returned to the local tissue bank.  

     
       
        
                                
 
 
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35 
 
 
13 DATA MANAGEMENT 
 
13.1 
Data Recording and Storage 
All data except for the PET/CT scans performed at the Imperial College London Imaging 
Facility will originate in the NHS. The principal means of data collection from patient visits 
will be imaging PET/CT data obtained at either Imperial College Healthcare NHS Trust or 
Imperial College London. Imaging PET/CT data from the Imperial College London Imaging 
Facility will be uploaded to Imperial CIF XNAT. Other screening visit and follow up data 
will be collected on paper CRFs. Data will be pseudonymised and then stored on Imperial 
College secure servers and on encrypted drives in accordance with the data protection 
act. All data will be linked pseudonymised prior to being analysed and stored for 10 years. 
Patient clinical, follow-up and imaging data  will then be inputted into  an electronic 
database (excel spreadsheet) held on a secure, password protected computer within 
Imperial College Healthcare Trust.  
All paper/ manual study documentation including those with personal identifiers will be 
stored in an access controlled locked office within Imperial College London, and the 
Imaging Facilities at Imperial College Healthcare NHS Trust and Imperial College London 
Subject’s original consent forms will be kept in the study master file in a controlled entry 
secure office at  Imperial College London ( Hammersmith campus). A copy of the consent 
forms will be kept in a study master file locked in a secure office at CIF for governance 
purposes and will also be copied to the medical records. 
The Investigator must retain essential documents until notified by the Sponsor and at 
least for ten years after study completion. Documents should be stored in such a way that 
they can be accessed/data retrieved at a later date. The data for this study will be 
maintained on a secure, password protected Imperial College Healthcare Trust computer, 
with only authorised personnel having access to them. 
No study document will be destroyed without prior written agreement between the 
Sponsor and the CI. Should the CI wish to assign the study records to another party or 
move them to another location, written agreement must be obtained from the Sponsor. 
Data and images obtained from scans may be used in an anonymous form for future 
research, including that carried out by commercial healthcare companies.  

     
       
        
                                
 
 
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13.2 
Audits and inspections 
The study may be subject to inspection and audit by Imperial College London under their 
remit as sponsor, the Study Coordination Centre and other regulatory bodies to ensure 
adherence to GCP and the UK Policy Frame Work for Health and Social Care Research. 
13.3 
Disclosure of Data  
Information concerning the study, patent applications, processes, scientific data or other 
pertinent information is confidential and remains the property of the Sponsor. The 
investigator may use this information for the purposes of the study only. 
All data information obtained as a result of the study will be regarded as CONFIDENTIAL, 
at least until appropriate analysis and review by the investigator(s) is completed. 
 
14 STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through the Imaging 
research office, Imperial College London,  GN1, Commonwealth Building, Hammersmith 
Campus, Du Cane Rd, London, W12 0NN. 
 
15  PUBLICATION AND DISSEMINATION  
 
The results of the study will be written and will be submitted for publication to a suitable 
peer reviewed journal. Results may be presented at conferences and internally within the 
Sponsor institution. A final summary of results will be provided to the REC. All data will be 
anonymised for publication and no identifiable personal data will be used. 
Patients will have the opportunity of being informed when data is published, if they wish. 
 
 
 
 

     
       
        
                                
 
 
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37 
 
 
16 REFERENCES 
 
1. 
Powles T, Albiges L, Staehler M, Bensalah K, Dabestani S, Giles RH, Hofmann F, 
Hora M, Kuczyk MA, Lam TB, Marconi L, Merseburger AS, Fernández-Pello S, Tahbaz R, 
Volpe A, Ljungberg B, Bex A. Updated European Association of Urology Guidelines 
Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer. Eur 
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