Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 1:32 PM
Ignite Modification Date:
2025-12-24 @ 1:32 PM
NCT ID:
NCT02152995
Brief Summary:
This phase II trial studies how well trametinib works in increasing tumoral iodine incorporation in patients with thyroid cancer that has come back or spread to another place in the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help make treatment with iodine I-131 more effective.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the effect of trametinib on enhancing radioiodine (RAI) activity by determining the proportion of patients alive at 6 months without disease progression by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version \[v\]1.1) criteria following treatment with RAI in co-administration with trametinib. (Cohort A) II. To evaluate the effect of trametinib on enhancing RAI activity by determining the objective response rate (ORR) at 6 months following treatment with radioiodine (RAI) in co-administration with trametinib. (Cohort A) III. To determine the proportion of patients following trametinib therapy with increased tumoral iodine incorporation as quantified by iodine iodine-124 (I-124) positron emission tomography (PET)/computed tomography (CT) lesional dosimetry. (Cohort B)
SECONDARY OBJECTIVES:
I. To determine the proportion of patients following trametinib therapy with increased tumoral iodine incorporation as quantified with I-124 PET/CT lesional dosimetry. (Cohort A) II. To evaluate the safety/tolerability of trametinib with or without RAI. (Cohort A) III. To evaluate changes in thyroglobulin levels in patients treated with RAI. (Cohort A) IV. To explore potential correlations between genomic alterations present in the tumor and/or tumoral pharmacodynamic changes induced by trametinib to clinical outcomes. (Exploratory) (Cohort A) V. To evaluate the effect of trametinib on enhancing RAI activity by determining the ORR at 6 months following treatment with RAI in co-administration with trametinib. (Cohort B) VI. To evaluate the effect of trametinib on enhancing RAI activity by determining the proportion of patients alive at 6 months without disease progression by RECIST v 1.1 criteria following treatment with RAI in co-administration with trametinib. (Cohort B) VII. To evaluate the safety/tolerability of trametinib with or without RAI. (Cohort B) VIII. To evaluate changes in thyroglobulin levels in patients treated with RAI. (Cohort B) IX. To explore potential correlations between genomic alterations present in the tumor and/or tumoral pharmacodynamic changes induced by trametinib to clinical outcomes. (Exploratory) (Cohort B) X. Preliminary evaluation of best objective response (BOR) rate for patients treated with trametinib alone. (Exploratory) (Cohort C) XI. Preliminary evaluation of the proportion of patients following treatment with trametinib alive at 6 months without disease progression by RECIST v 1.1 criteria. (exploratory) (Cohort C) XII. To evaluate the safety/tolerability of trametinib. (Cohort C) XIII. To evaluate changes in thyroglobulin levels in patients treated with trametinib. (Cohort C) XIV. To explore potential correlations between genomic alterations present in the tumor and/or tumoral pharmacodynamic changes induced by trametinib to clinical outcomes. (Exploratory) (Cohort C) XV. To explore the impact of continued trametinib upon RAI avidity and efficacy. (Exploratory) (Cohort C)
OUTLINE: Patients with RAS gene mutations are assigned to Cohort A, while patients without BRAF/RAS gene mutations are assigned to Cohort B.
COHORT A: Patients undergo iodine I-124 PET/CT on day 5 of week 1. Beginning day 6, patients receive trametinib orally (PO) daily for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo second iodine I-124 PET/CT on week 5. If I-124 PET/CT shows enough iodine absorption, patients may receive iodine I-131 PO and continue receiving trametinib for another 2 days. If I-124 shows that the thyroid is not absorbing iodine, patients have the option to be assigned to Cohort C.
COHORT B: Patients undergo iodine I-124 PET/CT on day 5 of week 1. Beginning day 6, patients receive trametinib PO daily for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo second iodine I-124 PET/CT on week 5. If I-124 PET/CT shows enough iodine absorption, patients may receive iodine I-131 PO and continue receiving trametinib for another 2 days. If I-124 shows that the thyroid is not absorbing iodine, patients have the option to be assigned to Cohort C.
COHORT C: Patients may continue trametinib at the doctor's discretion and do not receive iodine I-131.
After completion of study treatment, patients are followed up for 30 days.
Study:
NCT02152995
Study Brief:
Protocol Section:
NCT02152995