Measuring Treatment Response in Metastatic Renal Cell Cancer Using FPIA PET/CT

• ClinicalTrials.gov Identifier: NCT04802824
• Recruitment Status: Not yet recruiting
• First Posted: March 17, 2021
• Last Update Posted: March 18, 2021
• Sponsor: Imperial College London
• Information provided by (Responsible Party): Imperial College London

Study Description

Brief Summary:

Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the kidney. At the time of diagnosis, as many as a fifth of patients have metastatic disease (mRCC). Despite advances in treatment, long-term survival rates remain poor. 18F-fluoropivalate ([18F]FPIA) is a new tracer that images short chain fatty acid (SCFA) uptake in tumours, a key component of fatty acid oxidation.

The aim of the study is to investigate longitudinal changes in [18F]FPIA uptake at baseline, at 4-6 weeks and at 12 weeks following treatment initiation in patients using tyrosine kinase inhibitors (TKI's), chemotherapy, immunotherapy, or combinations of these.

The investigators hypothesise that the import of [18F]FPIA-detectable SCFA into tumours is high and decreases with effective treatment.

Condition or disease	Intervention/treatment
Metastatic Renal Cell Carcinoma	Other: PET/CT

Detailed Description:

24 evaluable patients with radiological and/or histological evidence of mRCC and due to receive systemic therapy will be enrolled. The patients invited to participate in the study will provide written informed consent. Patients will only undergo [18F]FPIA positron emission tomography (PET)/computed tomography (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 at baseline, 4-6 weeks and 12 weeks post the commencement of treatment. Patients will have been treated as per standard of care, which may have included TKI's, chemotherapy, immunotherapy or combinations of these. 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 and undergo whole body PET/CT scanning from 60 minutes.

Archival tumour biopsies (primary or metastatic lesion), taken within 3 months of the 1st [18F]FPIA PET/CT scan will be retrieved for analysis where possible.

Study Design

• Study Type: Observational
• Estimated Enrollment: 24 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Determining the Magnitude of Change in [18F]FPIA-detectable Short Chain Fatty Acid Uptake in Metastatic Renal Cell Cancer Following Therapy
• Estimated Study Start Date: April 2021
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: August 2024

Groups and Cohorts

Intervention Details:

• Other: PET/CT
  18F-fluoropivalate PET/CT scan.
  Other Name: Imaging Scan

Outcome Measures

Primary Outcome Measures :

1. Quantitative longitudinal measurement of [18F]FPIA uptake in mRCC. [ Time Frame: Baseline, 4-6 weeks and 12 weeks post-commencement of treatment. ]
   PET/CT

Secondary Outcome Measures :

1. Quantitative measurement of FPIA in healthy tissue including kidneys. [ Time Frame: Baseline, 4-6 weeks and 12 weeks post-commencement of treatment. ]
   PET/CT
2. 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. [ Time Frame: Baseline, 4-6 weeks and 12 weeks post-commencement of treatment. ]
   Routine Imaging Scans - Determined by the NHS Treating Clinician.

Other Outcome Measures:

1. [18F]FPIA uptake versus Foundation Medicine mutational signature test (Tumour Mutational Burden (TMB)) on biopsy material. [ Time Frame: Through study completion, an average of 3 years. ]
   Foundation Medicine mutational signature test.
2. [18F]FPIA uptake versus serum or urine carnitine/carnitine ester signature. [ Time Frame: Through study completion, an average of 3 years. ]
   Serum and urine carnitine analysis at external laboratory.

Biospecimen Retention:   Samples With DNA

Archival tumour biopsies from the primary or metastatic lesion, taken within 3 months of the first [18F]FPIA PET/CT scan.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with radiological and/or histological evidence of mRCC and due to receive systemic therapy.

Criteria

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 (outside of the liver).
3. The subject has an available diagnostic tumour biopsy of the primary and/or metastatic lesion taken within 3 months of 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 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.

Contacts and Locations

Contacts

Contact: Preetha Aravind, MBBS MD MRCP; 0203 313 3720; preetha.aravind@nhs.net

Contact: Laura McLeavy, MSc; 0203 313 3720; laura.mcleavy13@imperial.ac.uk

Locations

United Kingdom

Imperial College Healthcare NHS Trust/Imperial College London

London, United Kingdom, W12 0HS

Contact: Preetha Aravind, MBBS MRCP 0203 313 3720 preetha.aravind@nhs.net

Contact: Laura McLeavy, MSc 0203 313 3720 laura.mcleavy13@imperial.ac.uk

Principal Investigator: Naveed Sarwar, MBBS MRCP

Sub-Investigator: Preetha Aravind, MBBS MRCP

Sponsors and Collaborators

Imperial College London

More Information

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT04802824
• Other Study ID Numbers: 20CX6143
• First Posted: March 17, 2021
• Last Update Posted: March 18, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

PET/CT; Fatty Acid Oxidation

Additional relevant MeSH terms:

Carcinoma, Renal Cell; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases