Dabrafenib and Lapatinib Ditosylate in Treating Patients With Refractory Thyroid Cancer That Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT01947023|
Recruitment Status : Recruiting
First Posted : September 20, 2013
Last Update Posted : November 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|BRAF V600E Mutation Present BRAF V600K Mutation Present Metastatic Thyroid Gland Carcinoma Unresectable Thyroid Gland Carcinoma||Drug: Dabrafenib Other: Laboratory Biomarker Analysis Drug: Lapatinib Ditosylate Other: Pharmacological Study||Phase 1|
I. To determine the maximum tolerated dose of lapatinib (lapatinib ditosylate) that can be used in combination of dabrafenib.
I. To observe and record anti-tumor activity. II. Evaluate potential mechanisms of primary resistance of v-raf murine sarcoma viral oncogene homolog B (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 ditosylate.
Patients receive dabrafenib orally (PO) twice daily (BID) on days 1-28 and lapatinib ditosylate PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: Patients also receive dabrafenib PO for 2 weeks prior to beginning treatment with lapatinib ditosylate.
After completion of study treatment, patients are followed up for 4 weeks and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Dabrafenib in Combination With Lapatinib in BRAF Mutant Thyroid Cancer|
|Actual Study Start Date :||August 29, 2013|
|Estimated Primary Completion Date :||December 31, 2019|
Experimental: Treatment (lapatinib ditosylate, dabrafenib)
Patients receive dabrafenib* PO BID on days 1-28 and lapatinib ditosylate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients also receive dabrafenib PO for 2 weeks prior to beginning treatment with lapatinib ditosylate.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Lapatinib Ditosylate
Other Name: TykerbOther: Pharmacological Study
- Maximum tolerated dose (MTD) of lapatinib ditosylate, in combination with the established dose of dabrafenib, defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity [ Time Frame: First 42 days of treatment ]MTD is defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity.
- Mean percent change in the post-treatment tissues relative to pre-treatment tissues for the phosphorylated protein targets examined [ Time Frame: Baseline to day 7 of course 1 ]Tissues such as phosphorylated mitogen-activated protein kinase 1 (ERK), human epidermal growth factor receptor (HER) 2, HER3, epidermal growth factor receptor (EGFR), platelet derived growth factor (PDGF), or protein kinase B (AKT) will be examined. Mean percent change will be calculated and compared.
- Mean percentage change in transcript levels in the post-treatment tissues relative to pre-treatment tissues for several genes analyzed by reverse-transcriptase-polymerase chain reaction [ Time Frame: Baseline to day 7 of course 1 ]Genes including sodium/iodide symporter (NIS), dual-specificity phosphatase 5 (DUSP5), and plasminogen activator (PLAT) will be examined. Mean percentage change is calculated and compared with respect to each genotype.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01947023
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Eric J. Sherman 212-639-7202 email@example.com|
|Principal Investigator: Eric J. Sherman|
|Principal Investigator:||Eric Sherman||Memorial Sloan Kettering Cancer Center|