Radio Iodine Refractory Thyroid Cancer
Conditions
Interventions
Trade Name: Mekinist ®
Product Name: Mekinist®
Product Code: EU/1/14/931/06
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TRAMETINIB
CAS Number: 871700-17-3
Other descriptive name: MEKI
Sponsors
University Hospital Essen (Anstalt des öffentlichen Rechts)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must have histologically or cytologically confirmed progressive radioiodine refractory metastatic thyroid carcinoma of follicular origin (including papillary and its respective variants). • Confirmation in a certified laboratory of the mutation status of BRAF gene (primary tumor, recurrent tumor, or metastasis) . • Patients for whom a systemic treatment with sorafenib or lenvatinib or a chemotherapy is not considered and/or who refused to take either of these drugs within the next 6 months. • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as = 15 mm with CT scan, MRI, or calipers by clinical exam. Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment. • RAI-refractory disease on structural imaging, defined as any one of the following: 1) A metastatic lesion that is not radioiodine-avid on a diagnostic or therapeutic radioiodine scan performed less than 1 year prior to enrollment in the current study, or 2) Morphologically progressive or stable disease despite adequate RIT at least 6 month prior to enrollment in the current study There are no size limitations for the index lesion used to satisfy this entry criterion. • No recent treatment for thyroid cancer as defined as: 1) No prior 131I therapy is allowed 1.5x109/L • Hemoglobin = 9 g/dL • Platelets = 100 x 109/L • Albumin = 2.5 g/dL • Total bilirubin = 1.5x institutional ULN • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2x institutional ULN unless it is related to the primary disease • creatinine = 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) = 50 mL/min OR 24-hour urine creatinine clearance = 50 mL/min • Negative pregnancy test within 7 days prior to starting the study premenopausal women. Women of non-childbearing potential may be included without pregnancy test if they are either surgically sterile or have been postmenopausal for = 1 year. • Fertile men and women must use an effective
Exclusion criteria
Exclusion criteria: • Concomitant malignancies or previous malignancies within the last 3 years. Exception: Patients who have been disease-free for 3 years, patients with a history of completely resected non-melanoma skin cancer, and/or patients with indolent secondary malignancies, are eligible. • Use of other investigational drugs within 28 days preceding the first dose of drug treatment during this study. • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib and/or to dabrafenib . • History or evidence of cardiovascular risk including any of the following: • History or evidence of current, clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to the initiation of therapy on this protocol are eligible). • History of acute coronary syndromes (specifically, myocardial infarction and unstable angina), severe/unstable angina, coronary angioplasty, or stenting within 6 months prior to the initiation of therapy on this protocol. • History of symptomatic congestive heart failure within 6 months prior to the initiation of therapy on this protocol. • History of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocol. • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. • Pregnant, lactating, or breast feeding women. • Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone). • Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration. Those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration. • Unwillingness or inability to comply with study and follow-up procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a 35 patient pilot study (n=25 patients in the in BRAF wild type arm and n=10 patients in the BRAFV600E mutant arm) testing the hypothesis that the inhibition of MEK can restore iodine incorporation in BRAF wild type (WT) and a combined inhibition of BRAF and MEK can restore iodine incorporation in BRAFV600E mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer;Secondary Objective: 1) To evaluate changes in thyroglobulin levels in treated patients. 2) To evaluate the safety/tolerability of trametinib and dabrafenib/trametinib combination therapy. ;Primary end point(s): To determine the proportion of patients with BRAF WT RAIR thyroid cancer in which trametinib and the proportion of patients with BRAF MUT (N-, H-, K-RAS mutant, RET/PTC rearrangement) RAIR thyroid cancer in which the combination-therapy of dabrafenib and trametinib can increase tumoral iodine incorporation sufficiently. ;Timepoint(s) of evaluation of this end point: the time point for evaluation of the primary endpoint is about three weeks after initiation of treatment with trametinib or with combination trametinib and dabrafenib | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To evaluate changes in thyroglobulin levels in treated patients. 2) To evaluate the safety/tolerability of trametinib and dabrafenib/trametinib combination therapy. ;Timepoint(s) of evaluation of this end point: the time point for second endpoint is six months after drug treatment | — |
Countries
Germany
Contacts
Public ContactDepartment of Nuclear Medicine
University Hospital Essen (Anstalt des öffentlichen Rechts)
Outcome results
None listed