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RecruitingLast updated: 2 February 2024

I-FIRST: This phase II trial will use Dabrafenib and/or Trametinib to enhance treatment for people with thyroid cancer who no longer respond to radioactive iodine (a standard treatment for people with this type of cancer)A Prospective, Multi-Centre Trial of TKI Redifferentiation Therapy in Patients With RAIR Thyroid Cancer (I-FIRST Study)

Clinical summary

Summary

This is a non-randomised, open-label study for adults with radioiodine refractory differentiated thyroid cancer with BRAF V600E or NRAS mutations. 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. During Days 1-30, participants with BRAF V600E mutations will then receive Dabrafenib (oral, 150mg twice daily) and Trametinib (oral, 2mg once daily); and participants with RAS mutations will receive Trametinib (oral, 2mg once daily). All participants will then receive 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.

Conditions

This trial is treating patients with radioiodine refractory thyroid cancer

Cancer

Head and Neck Cancers Head and Neck

Age

People18+

Phase

II

Trial Acronym

I-FIRST

More information

Trial Identifiers

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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 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.

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