Clinical trial NCT04922801: Optimising Molecular Radionuclide Therapy
Official title: OPTIMISING MOLECULAR RADIONUCLIDE THERAPY: The Role of Quantitative SPECT/CT & PET/CT and Radiation Dosimetry (SELFIE)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neuroendocrine Tumors
Hyperthyroidism
Thyroid Cancer
Thyroid Carcinoma
Keywords: MRT
Neuroendocrine tumours (NET)
177Lu-DOTATATE
SUV
Quantitative SPECT/CT
Thyroid cancer
I-131
Hyperthyrodism
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Guy's and St Thomas' NHS Foundation Trust
First posted: 2021-06-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Female and male patients undergoing molecular radionuclide therapy at GSTTFT using Lutetium-177 peptides for neuroendocrine tumour and I-131 for benign and malignant thyroid disease therapy will be invited to participate.

The total sample size is estimated as 60 patients divided as 20 for patients receiving 131I for hyperthyroidism, 20 patients for 131I for thyroid cancer and 20 patients for177Lu-DOTATATE for neuroendocrine tumours. This sample should allow sufficient quantitative and dosimetry data to explore the research questions. The range in the number of patients who will be studied is intended to mitigate uncertainty regarding continuing restrictions related to the COVID-19 Coronavirus pandemic.

Brief summary: This project will examine the role of the whole body, PET and SPECT imaging before, during and after radionuclide treatment for 177Lu-Dotatate therapy, whole body and SPECT imaging for 131-I for thyroid cancer therapy, and whole-body imaging for 131I for hyperthyroidism therapy. Whole-body and SPECT images will be linked to personal dosimeter readings to determine whether

* Current radiation protection advice for patients receiving radionuclide treatment is appropriate.
* Radiopharmaceutical retention and/or SUV change in patients undergoing repeated radionuclide treatments.
* Data combined from early (quantitative imaging) and late (whole-body dose rate measurements) could support individual treatment planning for patients undergoing repeated cycles of molecular therapy.

Detailed description: This cohort (retro- \& prospective) study will be conducted at Guy's and St Thomas' NHS Foundation Trust (GSTTFT) among patients undergoing MRT. Pre and post-therapy blood tests, treatment administration, whole body and SPECT/PET imaging will be undertaken in strict accordance with existing GSTTFT approved protocols for each type of treatment. With the exception of hyperthyroid patients receiving I-131 therapy, these procedures are all part of the standard of care at GSTT. Hyperthyroid patients will be required to have one whole-body scan at 24hrs post-therapy activity administration in addition to their standard care. This will not result in additional radiation exposure.

The decision to proceed with MRT will have been agreed upon at the relevant multidisciplinary meeting in accordance with current practice guidelines. Pre and post-therapy blood tests, whole body and SPECT/PET imaging will be followed as per current GSTTFT protocols. Patients will be asked to undertake the following:

1. Neuroendocrine tumour and thyroid cancer patients: 1-7 days treatment whole-body gamma camera and SPECT /CT scan. (Part of standard of care post-treatment monitoring at GSTTFT).

   \*Hyperthyroid patients: 24-hour post-treatment whole-body gamma camera scan. (Part of this research protocol, will not involve any additional radiation).
2. Record SELFIE reading for 28 days post-therapy using the sheet provided. (Part of this research protocol).
3. Complete feedback questionnaire. (Part of this research protocol). \*Benign thyroid disease patients only: Reasonable travel expenses for the cost of an additional hospital visit for post-treatment scans will be reimbursed from the nuclear medicine research fund SPF228. (Maximum reimbursement 50 £)

For the purpose of this study, two dosimetry methods will be used and compared.

1. Whole-body self-monitored retention measurements study (SELFIE study):

   A handheld radiation monitor (ATOMTEX model AT6130, Belarus) will be used to follow the time course of radioactivity clearance in each patient. The measurement device (SELFIE device) will be introduced to patients by a member of the medical physics team. Patients will be shown how to operate and record readings obtained and will also receive illustrated written instructions to build confidence. The devices are user friendly and patients will be asked to record the measurements twice daily using a diary sheet, typically taking about one minute to complete on each occasion. Measurement can begin immediately following administration and will continue for 28 days afterwards.

   Following MRT administration, a standard whole-body dosimetry measurement will be taken by a medical physicist at 1 and 2 meters distance. The patient will begin to take SELFIE readings at the same time under supervision so that their records can be compared with the physicists' results.

   After 28 days, patients will be asked to return the diary sheet and SELFIE monitor by post to GSTTFT in a pre-paid, pre-addressed envelope.

   On completion of the 28-day exercise, patients will be asked to complete and return a feedback questionnaire.

   The paper record of SELFIE readings will be reviewed by investigators from each patient for 28 days post-therapy. All imaging will be performed at GSTTFT by specialist Nuclear Medicine/PET staff.

   All acquired images will be reconstructed and analysed by investigators using HERMES software as described in section 13.3.
2. Imaging response assessment Planar Whole body, SPECT/CT and PET/CT images will be acquired to assess uptake patterns and, in the case of sequential treatments, uptake/retention changes. SPECT/CT, PET/CT and whole-body scans will be performed in accordance with existing protocols at Guy's and St. Thomas' NHS Foundation Trust. This will not result in additional radiation exposure. (Schedule illustrated in 16.1 Appendix).

The SUV of target and non-target tissues will be calculated from quantitative pre and post-therapy PET/CT and post-therapy SPECT/CT images. As a result, early tumour response and toxicity in patients undergoing molecular targeted radionuclide therapy can be studied.

Patient-led dose rate (SELFIE) data and imaging data will be integrated to compare whole-body retention and evaluate sequential dose rate changes after repeated treatments.

The quality of SELFIE data will be assessed against pre-specified standards (completeness of data collection, data deviation). Patient satisfaction will be evaluated from the feedback questionnaire.

Eligibility criteria: Inclusion Criteria:

* Patients receiving MRT (177Lu-Peptide for Neuroendocrine Tumours and 131I for Thyroid Cancer and Benign Hyperthyroidism).
* Women of childbearing potential must use a reliable method of contraception and have a documented negative pregnancy test immediately prior to MRT administration in accordance with routine clinical practice.
* Able to comply with treatment plans, scheduled visits, all study whole body, SPECT/CT \& PET/CT imaging and follow-up.
* Able to use a personalised dosimetry handheld device and record daily readings for 28 days post MRT.
* Willing and able to give informed consent.

Exclusion Criteria:

* Pregnant or breastfeeding women.
* Any other considerations that may make the patient unable to tolerate whole body, PET or SPECT scans.
* Inability to use a personalised dosimetry handheld device and record the daily reading for 28 days post MRT.
* Participants who are involved in current research or have recently been involved in any research prior to recruitment.

Primary outcomes:
measure: 20 patients with Lu-Dotatate MRT response to therapy outcome as Assessed by response evaluation criteria in solid tumours RECIST (version 1.1)
timeFrame: started from the day of MRT administration at cycle 1 and cycle 4. (Total 4 MRT cycles, each cycle length 8-12 weeks). each participant time frame 1 year.
measure: Whole-body gamma image time activity curve (TAC) versus patient-led external dose rate (SELFIE) TAC.
timeFrame: SELFIE: 28 days measurements post administration of MRT activity. and Whole-body image:24 hrs post administration of MRT activity.
Secondary outcomes:
measure: Patient-led external dose measurement (SELFIE) area under the curve (AUC) change between cycle 1 & 4 MRT
timeFrame: 1 year for Neuroendocrine tumours participants and 1 month for thyroid cancer and hyperthyroidism participants.
measure: MRT patients Acceptance of patient-led monitor (SELFIE)
timeFrame: 28 days post MRT activity administration.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas Hospitals Foundation Trust
Study officials:
affiliation: King's College London
name: Valerie Lewington, Professor
role: PRINCIPAL_INVESTIGATOR
References: