Trial Outcomes & Findings for Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (NCT NCT02152995)
NCT ID: NCT02152995
Last Updated: 2025-09-15
Results Overview
Cohort A only. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
At 6 months
Results posted on
2025-09-15
Participant Flow
Participant milestones
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
9
|
|
Overall Study
Participants Who Continued Treatment With Trametinib Only
|
5
|
2
|
|
Overall Study
COMPLETED
|
24
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer
Baseline characteristics by cohort
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 Participants
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.2 years
n=5 Participants
|
53.4 years
n=7 Participants
|
53.3 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
25 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 6 monthsCohort A only. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Percentage of Patients Progression Free at 6 Months Following Treatment With Trametinib and I-124 (Cohort A)
|
44 % of pts progression free at 6 months
|
—
|
PRIMARY outcome
Timeframe: At 6 monthsAn exact binomial stage design will be used to discriminate between true 6-month progression/death rates of 20% vs 50%, and between true ORR rates at 6 months of 5% and 25%. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Progression Free Survival (Cohort A)
Pts progression-free at 6 months
|
11 Participants
|
—
|
|
Progression Free Survival (Cohort A)
Pts who were not progression-free at 6 months
|
14 Participants
|
—
|
PRIMARY outcome
Timeframe: At 6 monthsWill be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. An exact binomial stage design will be used to discriminate between true 6-month ORR rates at 6 months of 5% and 25%. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Percentage With Objective Response (Complete Response or Partial Response) (Cohort A)
|
32 % of pts with confirmed partial response
|
—
|
PRIMARY outcome
Timeframe: Up to 6 months"Adequate increase" is defined as increasing iodine incorporation in thyroid cancer metastases to a predicted lesional absorbed radiation dose equal to or exceeding 2,000 cGy with the administration of \< 300 mCi RAI. Iodine incorporation is quantified with PET/CT lesional dosimetry.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Iodine Incorporation in Thyroid Cancer Metastases to a Predicted Lesional Absorbed Radiation Dose Equal to or Exceeding 2,000 cGy With the Administration of =< 300 mCi Radioiodine (RAI) (Cohort B)
Pts who met the lesional dosimetry threshold for I-131 therapy
|
4 Participants
|
—
|
|
Iodine Incorporation in Thyroid Cancer Metastases to a Predicted Lesional Absorbed Radiation Dose Equal to or Exceeding 2,000 cGy With the Administration of =< 300 mCi Radioiodine (RAI) (Cohort B)
Pts who did not meet the lesional dosimetry threshold for I-131 therapy
|
5 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 6 monthsWill be determined by treatment with trametinib in thyroid cancer metastases to a predicted lesional absorbed radiation dose equal to or exceeding 2,000 cGy with the administration of =\< 300 mCi radioiodine (RAI). Proportion of patients with an adequate increase will be reported, along with the corresponding exact 95% confidence interval.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Adequate Increase in Iodine Corporation (Cohort A)
Pts who met the lesional dosimetry threshold for I-131 therapy
|
15 Participants
|
—
|
|
Adequate Increase in Iodine Corporation (Cohort A)
Pts who did not meet the lesional dosimetry threshold for I-131 therapy
|
10 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to up to 6 monthsPopulation: Data were not collected
Wilcoxon signed rank test will be performed for paired samples to compare the thyroglobulin level before and after RAI treatment in the subset of patients treated with RAI.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 30 days after completion of treatmentWill be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Toxicities will be individually reported and summarized.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Number of Participants With Toxicity (Cohort A)
|
25 Participants
|
—
|
SECONDARY outcome
Timeframe: At 6 monthsWill be assessed by RECIST v1 1.1 criteria. An exact binomial stage design will be used to discriminate between true 6-month ORR rates at 6 months of 5% and 25%.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Percentage With an Objective Response (Complete Response or Partial Response) (Cohort B)
|
11 % of pts with confirmed partial response
|
—
|
SECONDARY outcome
Timeframe: At 6 monthsAssessed per RECIST v1.1. Will be estimated using 95% confidence intervals.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Percentage of Patients Alive Without Disease Progression (Cohort B)
|
44 % of pts progression free at 6 months
|
—
|
SECONDARY outcome
Timeframe: Baseline up to 6 monthsPopulation: Data were not collected
Will determine whether treatment with trametinib and RAI results in decreasing thyroglobulin. Will perform a Wilcoxon signed rank test for paired samples to compare the thyroglobulin level before and after RAI treatment in the subset of patients treated with RAI.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 30 days after completion of treatmentWill be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0. Toxicities will be individually reported and summarized. Beginning April 1, 2018, CTCAE v5.0 will be utilized for adverse event (AE) reporting.
Outcome measures
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 Participants
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Number of Participants With Toxicity (Cohort B)
|
9 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsPopulation: Data were not collected
Analyses will be descriptive.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsPopulation: Data were not collected
Analyses will be descriptive.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsPopulation: Data were not collected
Analyses will be descriptive.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsPopulation: Data were not collected
Analyses will be descriptive.
Outcome measures
Outcome data not reported
Adverse Events
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Serious events: 6 serious events
Other events: 25 other events
Deaths: 6 deaths
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
Serious events: 1 serious events
Other events: 9 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 participants at risk
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 participants at risk
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
4.0%
1/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Cardiac disorders
Ejection Fraction Decrease
|
0.00%
0/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
General disorders
Death NOS
|
24.0%
6/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
Other adverse events
| Measure |
Cohort A (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=25 participants at risk
Patients with RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
Cohort B (Iodine I-124 PET/CT, Trametinib, Iodine I-131)
n=9 participants at risk
Patients without BRAF/RAS gene mutations 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.
Computed Tomography: Undergo iodine I-124 PET/CT
Iodine I 124: Undergo iodine I-124 PET/CT
Iodine I-131: Given PO
Laboratory Biomarker Analysis: Correlative studies
Pharmacodynamic Study: Correlative studies
Positron Emission Tomography: Undergo iodine I-124 PET/CT
Trametinib: Given PO
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
4.0%
1/25 • Up to 1 year
|
22.2%
2/9 • Up to 1 year
|
|
Investigations
Alanine aminotransferase increased
|
28.0%
7/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Investigations
Alkaline phosphatase increased
|
16.0%
4/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
12.0%
3/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
16.0%
4/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
60.0%
15/25 • Up to 1 year
|
22.2%
2/9 • Up to 1 year
|
|
Eye disorders
Blurred vision
|
8.0%
2/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Gastrointestinal disorders
Constipation
|
8.0%
2/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
28.0%
7/25 • Up to 1 year
|
55.6%
5/9 • Up to 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
24.0%
6/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Nervous system disorders
Dysgeusia
|
16.0%
4/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
General disorders
Edema limbs
|
20.0%
5/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.0%
2/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
General disorders
Fatigue
|
56.0%
14/25 • Up to 1 year
|
22.2%
2/9 • Up to 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
4.0%
1/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
General disorders
Gen disorders & admin site conditions Other, spec
|
4.0%
1/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
8.0%
2/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Vascular disorders
Hypertension
|
32.0%
8/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
12.0%
3/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Gastrointestinal disorders
Nausea
|
40.0%
10/25 • Up to 1 year
|
33.3%
3/9 • Up to 1 year
|
|
Gastrointestinal disorders
Oral pain
|
4.0%
1/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
General disorders
Pain
|
4.0%
1/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/25 • Up to 1 year
|
22.2%
2/9 • Up to 1 year
|
|
Investigations
Platelet count decreased
|
32.0%
8/25 • Up to 1 year
|
44.4%
4/9 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.0%
2/25 • Up to 1 year
|
0.00%
0/9 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
48.0%
12/25 • Up to 1 year
|
11.1%
1/9 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
40.0%
10/25 • Up to 1 year
|
33.3%
3/9 • Up to 1 year
|
|
Gastrointestinal disorders
Vomiting
|
16.0%
4/25 • Up to 1 year
|
33.3%
3/9 • Up to 1 year
|
Additional Information
Dr. Alan Ho, MD, PhD
Memorial Sloan Kettering Cancer Center
Phone: 646-608-3774
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60