Ignite Creation Date:
2025-12-24 @ 5:07 PM
Ignite Modification Date:
2025-12-26 @ 1:19 AM
Study NCT ID:
NCT06440850
Status:
RECRUITING
Last Update Posted:
2025-12-05
First Post:
2024-04-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Vemurafenib and Cobimetinib for the Treatment of Patients With High Risk Differentiated Thyroid Carcinoma With BRAFV600E Mutation
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
PRIMARY OBJECTIVE:
I. 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:
I. 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.
V. 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.
I. 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:
I. 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.
V. 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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2024-02359 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 21522 | OTHER | City of Hope Medical Center | View | |
| P30CA033572 | NIH | None | https://reporter.nih.gov/quic… | View |