Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer
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
6 other identifiers
interventional
34
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2014
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 29, 2014
CompletedFirst Posted
Study publicly available on registry
June 2, 2014
CompletedStudy Start
First participant enrolled
August 14, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 25, 2021
CompletedResults Posted
Study results publicly available
December 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
February 5, 2027
ExpectedApril 13, 2026
February 1, 2026
7 years
May 29, 2014
May 26, 2022
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Percentage of Patients Progression Free at 6 Months Following Treatment With Trametinib and I-124 (Cohort A)
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
At 6 months
Progression Free Survival (Cohort A)
An 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
At 6 months
Percentage With Objective Response (Complete Response or Partial Response) (Cohort A)
Will 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.
At 6 months
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)
"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.
Up to 6 months
Secondary Outcomes (7)
Adequate Increase in Iodine Corporation (Cohort A)
Up to 6 months
Changes in Thyroglobulin
Baseline to up to 6 months
Number of Participants With Toxicity (Cohort A)
Up to 30 days after completion of treatment
Percentage With an Objective Response (Complete Response or Partial Response) (Cohort B)
At 6 months
Percentage of Patients Alive Without Disease Progression (Cohort B)
At 6 months
- +2 more secondary outcomes
Other Outcomes (4)
Expression and Phosphorylation of MAPK Signaling Pathway Proteins
Up to 6 months
Expression and Phosphorylation of Negative Feedback Loops Connected to the MAPK Pathway (Such as Human Epidermal Growth Factor 3)
Up to 6 months
Quantitative Levels of Messenger Ribonucleic Acid Transcripts for MAPK Regulated and Thyroid-specific Gene Products
Up to 6 months
- +1 more other outcomes
Study Arms (3)
Cohort A (iodine I-124 PET/CT, trametinib, iodine I-131)
EXPERIMENTALPatients 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.
Cohort B (iodine I-124 PET/CT, trametinib, iodine I-131)
EXPERIMENTALPatients 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.
Cohort C (trametinib)
EXPERIMENTALPatients may continue trametinib at the doctor's discretion and do not receive iodine I-131.
Interventions
Undergo iodine I-124 PET/CT
Undergo iodine I-124 PET/CT
Given PO
Correlative studies
Correlative studies
Undergo iodine I-124 PET/CT
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, or poorly differentiated subtypes and their respective variants); confirmation of thyroid carcinoma will be done at Memorial Sloan-Kettering (MSK)
- 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 \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan, magnetic resonance imaging (MRI), or calipers by clinical exam; tumors in previously irradiated fields may be considered measurable if there is evidence of tumor progression after radiation treatment
- RAI-refractory disease on structural imaging, defined as any one of the following:
- A metastatic lesion that is not radioiodine-avid on a diagnostic radioiodine scan performed prior to enrollment in the current study, or
- A radioiodine-avid metastatic lesion which remained stable in size or progressed despite radioiodine treatment 6 months or more prior to entry in the study; there are no size limitations for the index lesion used to satisfy this entry criterion
- The presence of at least one fluorodeoxyglucose (FDG) avid lesion
- No recent treatment for thyroid cancer as defined as:
- No prior RAI therapy is allowed \< 6 months prior to initiation of therapy on this protocol; a diagnostic study using \< 10 millicurie (mCi) of RAI is not considered RAI therapy
- No external beam radiation therapy \< 4 weeks prior to initiation of therapy on this protocol; (previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol)
- No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed \< 4 weeks prior to the initiation of therapy on this protocol
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 3 months
- Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
- All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grade =\< 1 (except alopecia); grade 2 prior treatment related toxicities may be allowed after discussion with the principal investigator
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
- +20 more criteria
You may not qualify if:
- History of another malignancy; 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; MSK can consult the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above
- History of interstitial lung disease or pneumonitis
- Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib and during the 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, or excipients or to dimethyl sulfoxide (DMSO) or to thyrotropin alpha (Thyrogen)
- Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
- Other anti-cancer therapy while on study; (note: megestrol \[Megace\] if used as an appetite stimulant is allowed; thyroid-stimulating hormone \[TSH\] suppressive therapy is also allowed; palliative radiation therapy to non-target lesions is also allowed)
- Concurrent treatment with bisphosphonates is permitted; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
- Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], gingko biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng)
- Patients with the following ophthalmological findings/conditions:
- Intraocular pressure \> 21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure)
- Current or past history of central serious retinopathy or retinal vein occlusion
- History or evidence of cardiovascular risk including any of the following:
- Left ventricular ejection fraction (LVEF) \< LLN
- A QT interval corrected for heart rate using the Bazett's formula (QTcB) \>= 480 msec
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Alan Ho, MD, PhD
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Alan L Ho
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 29, 2014
First Posted
June 2, 2014
Study Start
August 14, 2014
Primary Completion
August 25, 2021
Study Completion (Estimated)
February 5, 2027
Last Updated
April 13, 2026
Results First Posted
December 28, 2022
Record last verified: 2026-02