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

NCT06440850 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 21522NCI-2024-02359P30CA033572
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Thyroid Gland Oncocytic Carcinoma; Thyroid Gland Papillary Carcinoma; Thyroid Gland Follicular Carcinoma

Outcome Measures

Primary Outcomes (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

  Up to completion of 6 week vemurafenib and cobimetinib therapy

Secondary Outcomes (4)

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

  Up to completion of 6 week vemurafenib and cobimetinib therapy

• Incidence of treatment related adverse events

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

• Progression free survival

  Up to one year after treatment

• Changes in thyroglobulin levels

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

Study Arms (1)

Treatment (vemurafenib and cobimetinib)

EXPERIMENTAL

Patients 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.

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

Interventions

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Treatment (vemurafenib and cobimetinib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (vemurafenib and cobimetinib)

Diagnostic Imaging PROCEDURE

Undergo I-123 diagnostic scan

Also known as: Medical Imaging

Treatment (vemurafenib and cobimetinib)

I-131 Uptake Test PROCEDURE

Undergo I-131 whole body scan

Also known as: I 131 Uptake, I-131 Uptake and Scan, Radioactive Iodine Uptake

Treatment (vemurafenib and cobimetinib)

Iodine I-131 RADIATION

Given PO

Also known as: 131-Iodine, Bound Iodide I-131, I 131, I-131, Iodide I-131, Iodide, I-131, Iodine 131, Iodine-131, Iodotope, Iodotrope

Treatment (vemurafenib and cobimetinib)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (vemurafenib and cobimetinib)

Recombinant Thyrotropin Alfa BIOLOGICAL

Given IM

Also known as: Recombinant Thyrotropin Alpha, Recombinant TSH Alpha, Thyrogen, Thyroid Stimulating Hormone Alpha, Thyrotropin Alfa, TSH-alpha

Treatment (vemurafenib and cobimetinib)

Ultrasound Imaging PROCEDURE

Undergo neck ultrasound

Also known as: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography, Ultrasound, Ultrasound Test, Ultrasound, Medical, US

Treatment (vemurafenib and cobimetinib)

Vemurafenib DRUG

Given PO

Also known as: BRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032, RG 7204, RG7204, RO 5185426, Zelboraf

Treatment (vemurafenib and cobimetinib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (vemurafenib and cobimetinib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (vemurafenib and cobimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma, Follicular; Thyroid Cancer, Papillary

Interventions

Specimen Handling; cobimetinib; X-Rays; Iodine-131; Magnetic Resonance Spectroscopy; Thyrotropin Alfa; Glycoprotein Hormones, alpha Subunit; High-Energy Shock Waves; Vemurafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma, Papillary; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Spectrum Analysis; Chemistry Techniques, Analytical; Thyrotropin; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chorionic Gonadotropin; Gonadotropins; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Ultrasonic Waves; Sound; Radiation, Nonionizing; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sasan Fazeli

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2024
• First Posted: June 4, 2024
• Study Start: July 15, 2024
• Primary Completion (Estimated): November 22, 2026
• Study Completion (Estimated): November 22, 2026
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (1)