NCT01947023

Dabrafenib and Lapatinib in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery

A Phase 1 Study of Dabrafenib in Combination With Lapatinib in BRAF Mutant Thyroid Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of lapatinib when given together with dabrafenib in treating patients with thyroid cancer that cannot be removed by surgery and has not responded to previous treatment (refractory). Dabrafenib selectively binds to and blocks the activity of v-raf murine sarcoma viral oncogene homolog B (BRAF), which may block the growth of tumor cells which contain a mutated BRAF gene. Lapatinib reversibly blocks the process in which a phosphate group is added to a molecule (phosphorylation) of the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (ErbB2), and the mitogen-activated protein kinase 3 (Erk-1) and mitogen-activated protein kinase 1(Erk-2) and protein kinase B (AKT) kinases. It also blocks cyclin D protein levels in human tumor cell lines. Dabrafenib and lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose of lapatinib that can be used in combination of dabrafenib. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Evaluate potential mechanisms of primary resistance of BRAF mutant thyroid cancer to dabrafenib by performing pathway profiling of tumor biopsies before and while on therapy. III. Obtain preliminary data on the activity of the combination of lapatinib and dabrafenib in BRAF mutant thyroid cancer through imaging. OUTLINE: This is a dose-escalation study of lapatinib. Patients receive dabrafenib orally (PO) twice daily (BID) on days 1-28 of each cycle. After two weeks of single agent dabrafenib, patients also start receiving lapatinib PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo tumor biopsy, blood sample collection, echocardiography (ECHO) or multigated acquisition scan (MUGA), as well as positron emission tomography (PET), computed tomography (CT), or magnetic resonance imaging (MRI) during screening and on study. After completion of study treatment, patients are followed up for 4 weeks and then annually thereafter.

Conditions

• Metastatic Thyroid Gland Carcinoma
• Unresectable Thyroid Gland Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Dabrafenib	Given PO
DRUG	Dabrafenib Mesylate	Given PO
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Lapatinib	Given PO
DRUG	Lapatinib Ditosylate	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
PROCEDURE	Positron Emission Tomography	Undergo PET

Timeline

• Start date: 2013-09-27
• Primary completion: 2026-06-01
• Completion: 2026-06-01
• First posted: 2013-09-20
• Last updated: 2025-11-05

Locations

1 site across 1 country: United States