There are 2 clinical trials
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.
Inclusion Criteria: - 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). --- K601E ---
- 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 - Patients with an injection of radio-contrast agent within 8 weeks prior enrolment - Previous history of retinal vein occlusion - Previous history of central serious retinopathy - Known hypersensitivity to the study drugs or to any of the excipients Inclusion Criteria: - 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). --- K601E ---
Description: Propotion of patients with a best overall response of Complete Response (CR) or a Partial Response (PR)
Measure: Objective Response Rate (ORR) Time: Evaluated 6 months after the first dose of trametinib or trametinib and dabrafenib followed by RAI treatment in each armsThe goal of this trial is to test the safety and efficacy of an innovative combination aimed to more profoundly inhibit ERK signaling in tumors.
- Patient's tumor must harbor an activating BRAF mutation (listed in Table 4 or approved by the study Principal Investigator) or a fusion involving the kinase domain of BRAF - Mechanistically validated activating non-V600 BRAF mutants - P367L/S - G464V/E - G469A/V/R - L485W - N486_A489delinsK - N486_P490del - E586K - L597Q/V/S - T599TT/TS - T599I/K - V600_K601delinsE - K601E/N/T - K601_S602delinsNT - BRAF kinase duplication - Fusions involving BRAF kinase domain - Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 - Adequate bone marrow, organ function and laboratory parameters: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Hemoglobin (Hgb) ≥ 8 g/dL with or without transfusions - Platelets (PLT) ≥ 75 x 109/L without transfusions - AST and/or ALT ≤ 2.5 × upper limit of normal (ULN); patient with liver metastases ≤ 5 ×ULN - Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL (Note: Patients who have a total bilirubin level > 1.5 x ULN will be allowed if their indirect bilirubin level is ≤ 1.5 x ULN) - Serum Creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50 mL/min at screening - Adequate cardiac function: - left ventricular ejection fraction (LVEF) ≥ 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram - QTc interval ≤ 480 ms (preferably the mean from triplicate ECGs) - Able to take oral medications - Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up) - Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through 30 days after the last dose of study drug/treatmentif of childbearing potential (Note: Permitted contraception methods listed in Section 9.3 should be communicated to the patients and their understanding confirmed. --- P367L --- --- G464V --- --- G469A --- --- L485W --- --- E586K --- --- L597Q --- --- T599I --- --- K601E ---
Description: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5,
Measure: dose-limiting toxicities (DLTs) Time: 1 yearDescription: Per RECIST Version 1.1
Measure: objective response rate (Phase II) Time: 1 year