Vemurafenib and Cobimetinib for High-Risk Thyroid Cancer with BRAFV600E Mutation
This study is testing if two drugs, vemurafenib and cobimetinib, can help patients with high-risk differentiated thyroid cancer that has a specific genetic change called a BRAFV600E mutation. These drugs are kinase inhibitors, meaning they block a protein that helps cancer cells grow. The goal is to see if giving these drugs before radioactive iodine therapy improves treatment. Researchers will measure how many patients have an excellent or indeterminate (unclear) response to the treatment before radioactive iodine. You would need to be at least 18 years old, have this specific type of thyroid cancer, and the BRAFV600E mutation to join. The study plans to enroll 21 participants.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It is a Phase II trial, which typically involves a smaller number of participants (21 planned here) to further evaluate safety and effectiveness.
- What's involved
- You would take vemurafenib and cobimetinib orally for about 6 weeks, undergo blood draws, CT scans, and I-123 and I-131 scans. You would also receive radioactive iodine and other injections.
- Compensation
- Not stated in the trial record.
- Follow-up
- You would be followed for about 14 months. The primary outcome is measured up to the completion of 6 weeks of vemurafenib and cobimetinib therapy.
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NCT06440850
Vemurafenib and Cobimetinib for the Treatment of Patients With High Risk Differentiated Thyroid Carcinoma With BRAFV600E Mutation
Recruiting
PHASE2Ages 18+InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~21 participants
Updated 2026-02-02 on ClinicalTrials.gov
What's tested:Biospecimen CollectionCobimetinibComputed TomographyDiagnostic ImagingI-131 Uptake TestIodine I-131
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Patients who achieve excellent or indeterminate response with vemurafenib and cobimetinib treatment prior to radioactive iodine therapy
Measured over Up to completion of 6 week vemurafenib and cobimetinib therapy
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Sasan Fazeli · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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:
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
Exclusion
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
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)
What this trial measures
- Patients who achieve excellent or indeterminate response with vemurafenib and cobimetinib treatment prior to radioactive iodine therapyUp to completion of 6 week vemurafenib and cobimetinib 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