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Clinical Trial Details

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

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Trial Information

Broad Health Condition Thyroid Cancer

Specific Health Condition

Trial FocusTreatment

Recruitment Details

Recruitment status

Recruitment State

Royal North Shore Hospital
Royal Brisbane and Women's Hospital
Alfred Hospital
Sir Charles Gairdner Hospital

Phase of TrialPhase 2

Trial 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


Key inclusion criteria

Inclusion Criteria:

    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 Criteria:

    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

    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.

Minimum age18 Years


Can Healthy volunteers participate? No

Contact details and further information

Sponsor Primary Sponsor Type: Other
Primary Sponsor Name: Olivia Newton-John Cancer Research Institute

Trial website

Trial IDNCT05182931

Contact person for information and recruitment