Efficacy of MEK (Trametinib) and BRAFV600E (Dabrafenib) Inhibitors With Radioactive Iodine (RAI) for the Treatment of Refractory Metastatic Differentiated Thyroid Cancer

NCT03244956 | Completed Phase 2

• 2 other identifiers: 2017-000742-212017/2527
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentric prospective non-randomized phase II trial, with two independent arms: one for patients with RAS mutation and one for patients with BRAFV600E mutation.

Conditions

Metastatic Radioactive Iodine Refractory Thyroid Cancer Patients With RAS or BRAF Mutation

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Propotion of patients with a best overall response of Complete Response (CR) or a Partial Response (PR)

  Evaluated 6 months after the first dose of trametinib or trametinib and dabrafenib followed by RAI treatment in each arms

Study Arms (2)

patients with RAS mutation

EXPERIMENTAL

Drug: Trametinib; Radiation: 131I; Drug: rhTSH

patients with BRAFV600E mutation

EXPERIMENTAL

Drug: Trametinib; Drug: Dabrafenib; Radiation: 131I; Drug: rhTSH

Interventions

Dabrafenib DRUG

150mg twice daily

patients with BRAFV600E mutation

131I RADIATION

5.5 GBq

patients with BRAFV600E mutation; patients with RAS mutation

rhTSH DRUG

0.9mg on two consecutive days after 35 days of treatment

patients with BRAFV600E mutation; patients with RAS mutation

Trametinib DRUG

2mg daily for a maximum of 6 weeks of treatment

patients with BRAFV600E mutation; patients with RAS mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with thyroid carcinoma of follicular origin (papillary, follicular or poorly differentiated and their respective variants)
• Known positive RAS (NRAS or KRAS or HRAS) or BRAFV600E or K601E mutation (determined on a previous analysis and/or on a representative formalin-fixed paraffin embedded (FFPE) tumor samples sent for central testing or on a biopsy sample sent for central testing).
• Radioiodine-refractory disease defined by at least one of the following item:
• Distant metastasis without radioiodine uptake on a posttherapeutic radioactive scan
• Distant metastasis disclosing RECIST progression within 12 months after a RAI treatment
• Measurable disease with at least one lesion \>/= 1.0 cm in the longest diameter for a non-lymph node or \>/= 1.5 cm in the short axis for a lymph node, measured with spiral computed tomography (CT) without iv contrast injection or magnetic resonance imaging (MRI) according to RECIST 1.1
• Progressive disease according to RECIST 1.1 criteria within 18 months prior initiation of treatment
• Absence of metastatic lesion \> 30mm
• Previous cumulated activity of radioactive iodine ≤ 600 mCi (22.2GBq)
• Patients may have received prior treatment with either 1 line of Tyrosine Kinase Inhibitor or 1 line of immunotherapy (excluding anti BRAF or anti MEK treatment such as sorafenib, dabrafenib, trametinib and selumitinib) but should be off treatment within 28 days prior to treatment start
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Blood pressure (BP) ≤ 140/90 mm Hg at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1
• Creatinine clearance ≥50 mL/min according to the Cockcroft and Gault formula
• Adequate bone marrow function with :
• Absolute neutrophil count (ANC) ≥1.5 x 109/L

You may not qualify if:

• Undifferentiated or Medullary (MTC) carcinoma of the thyroid
• Brain metastases (including asymptomatic brain metastases)
• Major surgery within 4 weeks prior to the first dose of drug
• Subjects having \> 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24 h will be ineligible.
• Prior RAI therapy \< 6 months prior initiation of treatment
• External beam radiation \< 4 weeks prior initiation of treatment
• Iodine contamination defined by a urine ioduria ≥ 50 μg/dl
• Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of the drugs
• History of congestive heart failure greater or equal to than New York Heart association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of drug, or cardiac arrhythmia associated with significant cardiovascular impairment and uncontrolled hypertension
• Electrocardiogram (ECG) with QT interval (QTc) interval ≥480 msec
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 2 months prior to the first dose of drug and any other active bleeding, coagulopathy or pathologic condition that would confer a high risk of bleeding.
• Active infection requiring systemic therapy
• Active malignancy (except for DTC, or definitively treated melanoma insitu, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months
• Any history of or concomitant medical condition that, in the opinion of the investigator, would compromise subject's ability to safely complete the protocol
• Females who are pregnant or breastfeeding

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val de Marne, 94805, France

Location

Related Publications (2)

• Anizan N, Pignard A, Borget I, Lamartina L, Schlumberger M, Broggio D, Leboulleux S, Lamart S. Lesional dosimetry in 131I refractory metastatic differentiated thyroid cancer with BRAFp.V600E or RAS mutation treated with trametinib +/- dabrafenib followed by radioactive iodine. Phys Med. 2026 Mar 19;145:105769. doi: 10.1016/j.ejmp.2026.105769. Online ahead of print.

  PMID: 41861727 DERIVED

• Leboulleux S, Benisvy D, Taieb D, Attard M, Bournaud C, Terroir-Cassou-Mounat M, Lacroix L, Anizan N, Schiazza A, Garcia ME, Ghuzlan AA, Lamartina L, Schlumberger M, Godbert Y, Borget I. MERAIODE: A Phase II Redifferentiation Trial with Trametinib and 131I in Metastatic Radioactive Iodine Refractory RAS Mutated Differentiated Thyroid Cancer. Thyroid. 2023 Sep;33(9):1124-1129. doi: 10.1089/thy.2023.0240. Epub 2023 Jul 26. No abstract available.

  PMID: 37350119 DERIVED

MeSH Terms

Interventions

trametinib; dabrafenib; Thyrotropin Alfa

Intervention Hierarchy (Ancestors)

Thyrotropin; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicentric prospective non-randomized phase II trial, with two independent arms: one for patients with RAS mutation and one for patients with BRAFV600E mutation

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: August 10, 2017
• Study Start: December 27, 2017
• Primary Completion: May 23, 2022
• Study Completion: January 15, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

FR (1)