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Thyroid CarcinomaEarly Phase 1NCT02145143

Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI-Refractory Thyroid Cancers With the BRAF Inhibitor Vemurafenib: A Pilot Study

A Early Phase 1 study testing Vemurafenib, serial 124I PET/CT and thyrotropin alpha in people with Thyroid Carcinoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to find out what effects, good and/or bad, a drug called vemurafenib, either alone or combined with another treatment called radioactive iodine, has on the patient and thyroid cancer. It is not known if vemurafenib works against thyroid cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Carcinoma
What is being tested?
Vemurafenib, serial 124I PET/CT and thyrotropin alpha
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
20 May 2014to 21 Nov 2024
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, or poorly differentiated subtypes and their respective variants).
  • Confirmation in a CLIA certified laboratory or in an FDA-approved assay that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600.
  • 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 CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. 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:
  • A metastatic lesion that is not radioiodine-avid on a diagnostic radioiodine scan performed up to 2 years 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.
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  • The presence of at least one fluorodeoxyglucose (FDG) avid lesion with a SUVmax ≥ 5.
  • No recent treatment for thyroid cancer as defined as:
  • No prior 131I therapy is allowed < 6 months prior to initiation of therapy on this protocol. A diagnostic study using < 10 mCi of 131I is not considered 131I 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.
  • Age ≥ 18 years.
  • ECOG performance status ≤ 2 (or 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 CTCAE v4.0 grade ≤ 1 (except alopecia). Grade 2 prior treatment related toxicities may be allowed after discussion with the Principal Investigator.
  • Patients must have normal organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) ≥ 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 method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patients must agree to undergo two research biopsies of a malignant lesion. Patients may be exempt from biopsy if 1) the investigator or person performing the biopsy judges that no tumor is accessible for biopsy, 2) the investigator or person performing the biopsy feels that the biopsy poses too great of a risk to the patient, or 3) the patient's platelet count is <100,000/mcl or he/she can not be safely removed from anti-coagulation therapy (if the anti-coagulation therapy needs to be temporarily held for the biopsy procedure). If the only tumor accessible for biopsy is also the only lesion that can be used for RECIST v1.1 response evaluation, then the patient may be exempt from biopsy. The goal will be to have a minimum of 3 patients undergo one or both of these research biopsies. Accrual may be limited only to subjects whose tumor is safely accessible for biopsy to ensure the accrual goal for research biopsies described above is met (e.g., if 7 of 10 patients are accrued without any biopsies having been obtained, then all subsequent subjects who are registered must qualify for attempted research biopsy in order to be enrolled.)
  • Availability of archival tumor tissue from the thyroid cancer primary or metastasis (a tissue block or a minimum of 30 unstained slides would be required. Patients with less archival tissue available may still be eligible for the study after discussion with the MSK Principal Investigator.)

Who cannot join

  • 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 vemurafenib 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 vemurafenib or thyrotropin alpha (Thyrogen).
  • History or evidence of cardiovascular risk including any of the following:
  • Corrected QT (QTc) interval ≥ 450 msec at baseline or history of congenital long QT syndrome or uncorrectable electrolyte abnormalities
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

The purpose of this study is to find out what effects, good and/or bad, a drug called vemurafenib, either alone or combined with another treatment called radioactive iodine, has on the patient and thyroid cancer. It is not known if vemurafenib works against thyroid cancer. This study will test in a small number of patients if it can be used with radioactive iodine to treat thyroid cancers. This type of study is called a pilot study. If the results are positive, a larger study with more patients may be done to further test this treatment.

Being tested
Vemurafenib, serial 124I PET/CT, thyrotropin alpha
Keywords
Radioiodine (RAI) Incorporation, Vemurafenib, 14-031
Medical subject headings
Thyroid Neoplasms, Heterotaxy Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VemurafenibDrug

    Also called RO5185426,, PLX4032, RG7204

  • serial 124I PET/CTDevice

  • thyrotropin alphaDrug

    Also called Thyrogen, Genzyme

Study groups in NCT02145143
Study groupRoleWhat they receive
thyroid cancer patientsExperimentalPatients will have lesional dosimetry with 124I PET/CT performed to quantify the baseline iodine avidity of index metastatic lesion(s). Patients will then receive vemurafenib (960 mg orally BID) for about 4 weeks, after which a second 124I PET/CT will be performed. For patients in whom the second 124I PET/CT demonstrates that > or = 2000 cGy can be achieved in at least one tumor with < 300 mCi of 131I, Thyrogen-stimulated standard dosimetry \& therapeutic 131I will be performed/administered concurrently with vemurafenib. The drug will then be discontinued \& tumor assessments will be conducted with serial radiologic scan(s) \& thyroglobulins (scans will be performed at baseline, before 131I, 3-4 months following 131I, \& 6 months after 131I). Patients whose tumors fail to demonstrate adequate iodine incorporation following vemurafenib to warrant 131I therapy, the study drug will be discontinued, a final tumor assessment will be performed, \& the patient will be taken off the study.
Receives: Drug: Vemurafenib; Device: serial 124I PET/CT; Drug: thyrotropin alpha

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Response

    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.

    Measured: 1 year

Secondary outcomes (2)

  1. objective response rate (ORR)

    To evaluate the effect of vemurafenib on enhancing 131I activity by determining the ORR by RECIST v1.1 criteria at 6 months following treatment with vemurafenib +/- 131I.

    Measured: 6 months

  2. safety

    Toxicities will be assessed through the NCI-Common Terminology Criteria for Adverse Events version 4.0, individually reported and summarized. Monitoring for vemurafenib-related toxicities will be continued until 30 days after the last dose of drug therapy.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2014 (estimated)
  2. Study start20 May 2014
  3. Primary completion21 Nov 2024
  4. Study completion21 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02145143
Sponsor's protocol ID
14-031
Status last verified
Nov 2024
First submitted
20 May 2014
Last updated
18 Jun 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Dunn LA, Sherman EJ, Baxi SS, Tchekmedyian V, Grewal RK, Larson SM, Pentlow KS, Haque S, Tuttle RM, Sabra MM, Fish S, Boucai L, Walters J, Ghossein RA, Seshan VE, Ni A, Li D, Knauf JA, Pfister DG, Fagin JA, Ho AL. Vemurafenib Redifferentiation of BRAF Mutant, RAI-Refractory Thyroid Cancers. J Clin Endocrinol Metab. 2019 May 1;104(5):1417-1428. doi: 10.1210/jc.2018-01478.

    PubMed 30256977

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Vemurafenib, serial 124I PET/CT and thyrotropin alpha in people with Thyroid Carcinoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02145143, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2025.

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