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Thyroid Gland Follicular CarcinomaPhase 2NCT06440850

Vemurafenib and Cobimetinib for the Treatment of Patients With High Risk Differentiated Thyroid Carcinoma With BRAFV600E Mutation

A Phase 2 study testing Biospecimen Collection, Cobimetinib and Computed Tomography in people with Thyroid Gland Follicular Carcinoma and Thyroid Gland Oncocytic Carcinoma, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase II trial tests how well vemurafenib and cobimetinib work in treating patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Cobimetinib and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
15 Jul 2024to 22 Nov 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Documented informed consent of the participant and/or legally authorized representative
  • Willingness to be followed for about 14 months
  • Males or females aged ≥ 18 years at the time of informed consent
  • Patients with thyroid carcinoma of follicular origin (papillary, follicular or Hurthle cell)
  • Known positive BRAFV600E mutation (determined on a previous analysis and/or on a representative formalin-fixed paraffin embedded (FFPE) tumor samples or on a biopsy sample)
  • High risk for recurrence according to the American Thyroid Association (ATA) guideline defined as having one or more of the features below:
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  • Gross extrathyroidal extension
  • FTC with extensive vascular invasion (> 4), although less likely to have BRAF mutation
  • PTC with vascular invasion
  • Advanced nodal disease of (any node >3 cm, > 4 nodes, or extra-nodal extension)
  • BRAF+TERT promoter mutation
  • Post op thyroglobulin (TG) suggestive of distant metastasis
  • Distant metastatic sites (only for exploratory arm)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Blood pressure (BP) ≤ 140/90 mm Hg at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to treatment start
  • Creatinine clearance ≥ 50 mL/min according to the Cockcroft and Gault formula
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100 x 109/L
  • Normal blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤ 1.5
  • Bilirubin ≤ 1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
  • Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5 × ULN if subject has liver metastases)
  • Women of childbearing potential must have a negative urine or serum β-HCG pregnancy test within 7 days prior to the administration of the first study treatment
  • Agreement by women of childbearing potential (WOCBP) and males of childbearing potential* to use an effective method of birth control for at least 3 months prior to screening through 1 year of study follow-up.
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • Effective birth control defined as hormonal and/or barrier contraception
  • Non-English speaking persons and adults lacking capacity to consent are not excluded from participation

Who cannot join

  • Prior RAI treatment
  • Prior anti-BRAF, anti-MEK treatment such as sorafenib, dabrafenib, vemurafenib, encorafenib, binimetinib, cobimetinib, trametinib, d selumitinib and other TKIs like, lenvatinib, sunitinib, axitinib, cabozantenib, vandatinib, pazopanib use
  • Low to intermediate risk differentiated thyroid cancer (DTC) cases (not having the high-risk features as described above)
  • RAI contraindication
  • Undifferentiated or Medullary (MTC) carcinoma of the thyroid
  • Major surgery within 4 weeks prior to the first dose of treatment
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  • Subjects having > 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥ 1 g/24 h will be ineligible
  • Need for locoregional treatment such as surgery, external beam radiation or thermoablation at inclusion
  • External beam radiation, for thyroid cancer, <4 weeks prior initiation of treatment
  • Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of the drugs
  • History of congestive heart failure greater or equal to than New York Heart association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of treatment, or cardiac arrhythmia associated with significant cardiovascular impairment and uncontrolled hypertension
  • Electrocardiogram (ECG) with QT interval (QTc) interval ≥ 480 msec
  • Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 2 months prior to the first dose of treatment and any other active bleeding, coagulopathy or pathologic condition that would confer a high risk of bleeding
  • Active infection requiring systemic therapy
  • Active malignancy (except for DTC, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months
  • Any history of or concomitant medical condition that, in the opinion of the investigator, would compromise subject's ability to safely complete the protocol
  • Females who are pregnant or breastfeeding
  • Patients with an injection of radio-contrast agent within 12 weeks prior to enrollment (can be enrolled after 12 weeks)
  • Previous history of retinal vein occlusion
  • Previous history of central serious retinopathy
  • Known hypersensitivity to the study drugs or to any of the excipients
  • Any other condition (including psychosocial condition) that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Any other condition that would confound study results
  • Noncompliance
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Sasan Fazeli, 626-256-4673 ext. 82251, sfazeli@coh.org

    Sasan Fazeli

    Recruiting

Other trials in United States

About this study

Official title: A Pilot Clinical Trial of Vemurafenib and Cobimetinib as a Redifferentiation Strategy in High-Risk, Radioactive Iodine (RAI) Naïve, BRAFV600E Mutated Differentiated Thyroid Carcinoma Patients Undergoing Initial RAI Therapy

This phase II trial tests how well vemurafenib and cobimetinib work in treating patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy. Vemurafenib and cobimetinib are used in patients whose cancer has a mutated (changed) form of a gene called BRAF. They are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving vemurafenib and cobimetinib may work better to treat patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy.

Read the detailed description

PRIMARY OBJECTIVE:

  1. The proportion of BRAF mutated high-risk differentiated thyroid carcinoma patients who achieve excellent or indeterminate response with vemurafenib and cobimetinib treatment prior to initial radioactive iodine (RAI) therapy as defined by American Thyroid Association guideline.

SECONDARY OBJECTIVES:

  1. The proportion of patients who had significant change on their I-123 scan before and after the targeted therapy.

II. To evaluate the safety and tolerability as determined by adverse events related to vemurafenib and cobimetinib combination therapy.

III. To evaluate the efficacy of vemurafenib and cobimetinib in enhancing RAI avidity by assessing the progression-free survival.

IV. To evaluate the diagnostic and prognostic value of thyroglobulin level as determined by thyroglobulin changes associated with treatment response.

  1. To evaluate the tumor molecular characteristics in treatment responders as compared to non-responders.

OUTLINE:

Patients receive vemurafenib orally (PO) twice per day (BID) for 6 weeks and cobimetinib PO once per day (QD) for 3 weeks, followed by 1 week off, and then continuing for 2 weeks. Patients then receive iodine 131 PO followed by 3 additional days of vemurafenib PO BID and cobimetinib PO QD. Patients receive thyrogen intramuscularly (IM) daily for 2 days followed by I-123 diagnostic scan during screening and on study. Patients also undergo magnetic resonance imaging (MRI) during screening, positron emission tomography (PET) scan or computed tomography (CT) scan and blood sample collection throughout the study and ultrasound imaging and I-131 whole body scan during follow up.

After completion of study treatment, patients are followed up every 3 months for up to 12 months.

Being tested
Biospecimen Collection, Cobimetinib, Computed Tomography, Diagnostic Imaging, I-131 Uptake Test
Medical subject headings
Adenocarcinoma, Follicular, Thyroid Cancer, Papillary

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • CobimetinibDrug

    Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Diagnostic ImagingProcedure or surgery

    Also called Medical Imaging

    Undergo I-123 diagnostic scan

  • I-131 Uptake TestProcedure or surgery

    Also called I 131 Uptake, I-131 Uptake and Scan, Radioactive Iodine Uptake

    Undergo I-131 whole body scan

  • Iodine I-131Radiation

    Also called 131-Iodine, Bound Iodide I-131, I 131, I-131

    Given PO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET scan

  • Recombinant Thyrotropin AlfaBiological

    Also called Recombinant Thyrotropin Alpha, Recombinant TSH Alpha, Thyrogen, Thyroid Stimulating Hormone Alpha

    Given IM

  • Ultrasound ImagingProcedure or surgery

    Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography

    Undergo neck ultrasound

  • VemurafenibDrug

    Also called BRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032

    Given PO

Study groups in NCT06440850
Study groupRoleWhat they receive
Treatment (vemurafenib and cobimetinib)ExperimentalPatients receive vemurafenib PO BID for 6 weeks and cobimetinib PO QD for 3 weeks, followed by 1 week off, and then continuing for 2 weeks. Patients then receive iodine 131 PO followed by 3 additional days of vemurafenib PO BID and cobimetinib PO QD. Patients receive thyrogen IM daily for 2 days followed by I-123 diagnostic scan during screening and on study. Patients also undergo MRI during screening, PET scan or CT scan and blood sample collection throughout the study and ultrasound imaging and I-131 whole body scan during follow up.
Receives: Procedure: Biospecimen Collection; Drug: Cobimetinib; Procedure: Computed Tomography; Procedure: Diagnostic Imaging; Procedure: I-131 Uptake Test; Radiation: Iodine I-131; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Recombinant Thyrotropin Alfa; Procedure: Ultrasound Imaging; Drug: Vemurafenib

What is being measured

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

  1. Patients who achieve excellent or indeterminate response with vemurafenib and cobimetinib treatment prior to radioactive iodine therapy

    Excellent and indeterminate responses are defined by 2015 American Thyroid Association Management Guildelines for Differentiated Thyroid Cancer:

    • Excellent: Negative imaging and either suppresed thyroglobulin < 0.2 ng/mL or TSH-stimulated thyroglobulin < 1 ng/mL
    • Indeterminate: Nonspecific findings on imaging studies, faint uptake in thyroid bed on RAI scans, nonstimulated thyroglobulin detectable, but <1 ng/mL, stimulated thyroglobulin detectable but <10 ng/mL or thyroglobulin antibodies stable or declining in the absence of structural or functional disease

    Measured: Up to completion of 6 week vemurafenib and cobimetinib therapy

Secondary outcomes (4)

  1. Proportion of patients who achieve increased iodine incorporation to a predicted lesion absorbed dose of 2000 cGy with I-131 dose of ≤ 300 mCi

    Measured: Up to completion of 6 week vemurafenib and cobimetinib therapy

  2. Incidence of treatment related adverse events

    Will be summarized by type, severity (by Common Terminology Criteria for Adverse Events version 5.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.

    Measured: Up to completion of 6 week vemurafenib and cobimetinib therapy and 3 days of post-radioactive iodine therapy

  3. Progression free survival

    From initiation of study therapy to the first observation of disease relapse/progression or death from any cause, whichever occurs first.

    Measured: Up to one year after treatment

  4. Changes in thyroglobulin levels

    Measured: Baseline, 3, 6, 9, months post-treatment up to one year

Timeline

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

  1. First posted4 Jun 2024
  2. Study start15 Jul 2024
  3. Primary completion22 Nov 2026 (estimated)
  4. Study completion22 Nov 2026 (estimated)

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
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06440850
Sponsor's protocol ID
21522
Other IDs
NCI-2024-02359, 21522, P30CA033572
Status last verified
Jan 2026
First submitted
19 Apr 2024
Last updated
2 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Cobimetinib and Computed Tomography in people with Thyroid Gland Follicular Carcinoma and Thyroid Gland Oncocytic Carcinoma, run by City of Hope Medical 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 27 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 2 Feb 2026. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patients who achieve excellent or indeterminate response with vemurafenib and cobimetinib treatment prior to radioactive iodine therapy (time frame: Up to completion of 6 week vemurafenib and cobimetinib therapy). 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 NCT06440850.

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 2 Feb 2026.

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