Ignite Creation Date:
2025-12-24 @ 1:32 PM
Ignite Modification Date:
2026-02-25 @ 7:21 PM
Study NCT ID:
NCT02152995
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-15
First Post:
2014-05-29
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 2 Study of Trametinib in Combination With Radioiodine (RAI) for RAS Mutant or RAS/RAF Wild-Type, RAI-Refractory Recurrent and/or Metastatic Thyroid Cancers
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2014-01106 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 13-157 | None | None | View | |
| 9446 | OTHER | Memorial Sloan Kettering Cancer Center | View | |
| 9446 | OTHER | CTEP | View | |
| P30CA008748 | NIH | None | https://reporter.nih.gov/quic… | View |
| P50CA172012 | NIH | None | https://reporter.nih.gov/quic… | View |
| R01CA184724 | NIH | None | https://reporter.nih.gov/quic… | View |