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

Sponsor
Olivia Newton-John Cancer Research Institute
Study ID
NCT05182931
Phase
PHASE2
Status
Unknown

Conditions

  • Thyroid Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Jul 14, 2022
Status verified
Oct 2023
Primary completion
Dec 30, 2024
Completion
Dec 30, 2025

Study Design

Enrollment
80 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: BRAFv600E mutant radioiodine refractory thyroid cancer
    Prior to commencing interventional treatment, participants will commence a low iodine diet and undergo thyroxine withdrawal and commence T3 replacement from day -27. On day -5 they will receive an oral dose of 124I (40MBq/1.08 mCi) with imaging at 24 hours (+/-6) post dose and a second imaging assessment within 120 hours. Participants will receive Dabrafenib (oral, 150mg BD) and Trametinib (oral, 2mg OD) from day 1-30. A second oral dose of I124 will be administered at day 24 followed by imaging at the same interval as baseline. Participants achieving \>20Gy tumour uptake of I124 will be administered 6GBq (3.3Gy/GBq) 131I, I131 wb scan and SPECT/CT will be performed within 24 hours and at hospital discharge. Participants who do not achieve \>20Gy tumour update of I-124 will move into follow up. Follow up will occur every 12 weeks for 12 months.
  • Experimental: RAS mutant radioiodine refractory thyroid cancer
    Prior to commencing interventional treatment, participants will commence a low iodine diet and undergo thyroxine withdrawal and commence T3 replacement from day -27. On day -5 they will receive an oral dose of 124I (40MBq/1.08 mCi) with imaging at 24 hours (+/-6) post dose and a second imaging assessment within 120 hours. Participants will receive Trametinib (oral, 2mg OD) from day 1-30. A second oral dose of I124 will be administered at day 24 followed by imaging at the same interval as baseline. Participants achieving \>20Gy tumour uptake of I124 will be administered 6GBq (3.3Gy/GBq) 131I, I131 wb scan and SPECT/CT will be performed within 24 hours and at hospital discharge. Participants who do not achieve \>20Gy tumour update of I-124 will move into follow up. Follow up will occur every 12 weeks for 12 months.

Primary Outcome Measure

Progression free survival as assessed by RECIST 1.1 criteria at 6 months in participants who proceed to I131 treatment [ Time Frame: At 6 months following day 1. ]

Central Contacts

Related Studies