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RecruitingLast updated: 6 October 2025

I-FIRST: This trial aims to use targeted therapy drugs to enhance treatment for people with thyroid cancer with NRAS or BRAFV600E mutations who no longer respond to standard treatment with radioactive iodineA Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study)

Clinical summary

Summary

You may be eligible for this study if you are aged 18 years and older, and have radioiodine refractory differentiated thyroid cancer with BRAF V600E or NRAS mutations.

About 3-4 weeks prior to commencing study treatment, all participants will have a PET/CT scan and commence a low iodine diet and thyroxine hormone withdrawl. 

About a week before treatment begins, all participants will receive 124I dose and another scan.

On day -5 they will receive an oral dose of iodine-124 which will be followed by further imaging and scans.

Participants will then begin a total of 30 days of treatment. Participants with BRAF V600E mutations will receive Dabrafenib (oral, 150mg twice daily) and Trametinib (oral, 2mg once daily); and participants with RAS mutations will receive Trametinib (oral, 2mg once daily).

On Day 23, all participants will then receive a second oral dose of idone-124 followed by further scans.

Participants achieving >20Gy tumour uptake of iodine-124 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 iodine-124 will move into follow up.

Follow up will occur every 12 weeks for 12 months, and then every 6 months until progression.

Conditions

This trial is treating patients with radioiodine refractory thyroid cancer

Cancer

Thyroid Cancer Thyroid

Age

People18+

Phase

II

Trial Acronym

I-FIRST

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Olivia Newton-John Cancer Research Institute

Scientific Title

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

Eligibility

Inclusion

  1. Histologically-confirmed differentiated (including poorly differentiated) thyroid cancer that is either locally advanced or metastatic.
  2. Age > 18 years.
  3. Life expectancy > 12 weeks.
  4. Documented radiological progression by RECIST 1.1 in last 12 months.

  5. Radioiodine refractory (at least one of):

    1. one measurable lesion without radioiodine uptake on 131I scan,
    2. at least one measurable lesion that had progressed by RECIST criteria within 12 months of 131I therapy despite 131I avidity at time of treatment, or
    3. cumulative treatment with >24 GBq (600 mCi) of 131I.
  6. At least one evaluable lesion as per RECIST v1.1 that has not been treated with local radiation therapy within 3 months prior to the first dose of TKI. Irradiated lesions can only be included as an evaluable lesion if it has shown radiological progression as per RECIST v1.1 on subsequent imaging following irradiation.
  7. NRAS or BRAF V600E mutation tested by NGS in a NATA accredited laboratory or by recognised sequencing platform.
  8. ECOG 0-1.
  9. Informed consent.

  10. Adequate haematological and biochemical parameters:

    1. Haemoglobin ≥ 9g/dL
    2. Neutrophils ≥ 1.5 x 109/L
    3. Platelets ≥ 100 x 109/L
    4. INR ≤ 1.4
    5. Serum Creatinine ≤ 1.3 x ULN
    6. Estimated Creatinine Clearance ≥ 30 ml/min (by Cockcroft Gault Formula)
    7. Serum ALT and AST ≤ 2.5 x ULN
    8. Serum Total Bilirubin ≤ 1.5 x ULN.
    9. TSH suppression <0.1mU/L or otherwise consistent with 2015 ATA Guidelines on Thyroid Cancer

Exclusion

  1. Anaplastic thyroid cancer.
  2. Suitable for curative surgery or radiotherapy.
  3. Other anti-cancer (including TKI) therapy in prior 6 weeks.
  4. Concurrent malignancy other than non-melanoma skin cancer. Prior malignancies treated with curative intent and no evidence of recurrence in past three years may be allowed upon discussion with the medical monitor.
  5. Unstable brain metastasis. Treated or non-treated brain metastasis are allowed if neurologically stable, asymptomatic, on a stable steroid dose for a period of 2 weeks, and not anticipated to require any intervention during the trial treatment period. If treated with radiation or surgery, any related AE's should have recovered to ≤ grade 1 prior to enrolment on trial.
  6. Pregnancy, breastfeeding or unwilling to use contraception in those of child-bearing age.
  7. Significant medical condition that would prevent compliance with study procedures.
  8. History of retinal vein occlusion or retinopathy.
  9. Iodine-containing contrast scan within 8 weeks of planned 124I scan.

Inclusion

  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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