NCT05182931

A Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study)

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Olivia Newton-John Cancer Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This prospective, multi-centre, open label, non-randomised phase II trial aims restore radioiodine sensitivity in patients with NRAS or BRAFV600E mutant refractory thyroid cancer. Participants will be treated with Trametinib +/- Dabrafenib tyrosine kinase inhibitors for a period of 30 days, restoration of sensitivity will be monitored using 18F-FDG-PET \& I-124 PET imaging.

Detailed description

This is a prospective, non-randomised, multi-centre study which will be conducted at 10 sites around Australia. Adult patients (18+ years) with radioiodine refractory differentiated thyroid cancer with BRAF V600E or NRAS mutant RECIST 1.1 evaluable tumours will be eligible to participate. . All eligible patients will undergo a 18F-FDG PET/CT scan during the registration period (day -28), followed by T4 withdrawal and low iodine diet. T3 will be administered after T4 withdrawal and for up to 10 days prior to the 124I dose to minimise symptoms of hypothyroidism. The first 124I dose will be administered orally at a dose of 40 MBq (1.08 mCi) on day -5 with a 18FDG-PET performed on the same day. Patients will then have 124I-PET imaging and bloods at 24 hrs (+/- 6 hrs) post-dose, with a second imaging time-point up until 120 hours post- 124I dose. The initial 124I study (pre-TKI) will serve as a baseline for the second 124I-PET (day 24, after 23 days of TKI), and demonstrate changes in NIS expression and radioiodine uptake as a result of TKI treatment. Patients will then commence a total of 30 days of treatment with the MEK TKI trametinib (for NRAS mutant tumours) or the MEK and BRAF V600E TKI combination of trametinib and dabrafenib (for BRAF V600E mutant tumours). Patients will then have a further 18F-FDG PET/CT scan and 124I dose on day 23, and scans for dosimetry (124I-PET) at 24 hrs (+/- 6 hrs) post-dose (day 24), with a second imaging time-point up until 120 hours post-124I administration. If at least one lesion shows uptake on 124I scans consistent with \> 20Gy / 6GBq (3.3Gy/GBq) 131I administered (based on the 24-hour scan), then 131I treatment will be administered on day 29. The dose of 131I administered will be fixed at 6 GBq (150 mCi) to allow for evaluation of dose response. TKI treatment will continue until the day after 131I treatment is given (total 30 days). Follow-up staging (CT) will occur every 3 months for the first 24 months, then every 6 months until progression, and 18F-FDG PET at 6 and 12 months. Non-stimulated thyroglobulin (Tg) will also be measured at 3, 6, 9 and 12 months, and evaluated as a percentage change from baseline. QoL and health economic data will be collected in all patients going on study. Overall survival will be obtained by long-term follow-up. Central review of tumour mutations, 124I PET dosimetry, staging (RECIST) and 18F-FDG PET (PERCIST) will be performed.

Conditions

• Thyroid Cancer

Interventions

Type	Name	Description
DRUG	Dabrafenib 75 MG	Refer arm description
DRUG	Trametinib 2 MG	Refer arm description

Timeline

• Start date: 2022-07-14
• Primary completion: 2024-12-30
• Completion: 2025-12-30
• First posted: 2022-01-10
• Last updated: 2023-10-31

Locations

9 sites across 1 country: Australia