Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436
Recruitment status was Recruiting
Radioactive iodine therapy is often part of the standard treatment for Papillary Thyroid Carcinoma (PTC) patients. However, in many patients, tumors develop a resistance or no longer respond to radioactive iodine therapy (iodine-refractory). Several lines of evidence suggest that blocking the BRAF gene may help to re-sensitize the tumors to radioactive iodine. BRAF is a protein that plays a central role in the growth and survival of cancer cells in some types of PTC. The investigational drug GSK2118436 may work by blocking the BRAF protein in cancer cells lines and tumors that have a mutated BRAF gene.
In this research study, the investigators are looking to see if GSK2118436 can re-sensitize iodine-refractory PTC to radioactive iodine therapy. The investigators are also looking at the safety of adding GSK2118436 to radioactive iodine therapy.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436|
- Radioiodine Uptake [ Time Frame: 2 years ] [ Designated as safety issue: No ]To explore the hypothesis that treatment with GSK2118436 in patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC will lead to increased radioiodine uptake in their disease sites (all patients).
- Feasibility [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the feasibility, as defined by the ability to enroll and treat the specified number of patients, of: (a) administering GSK2118436 for 28 days in patients with BRAF V600E-mutant PTC, prior to whole body iodine scanning (all patients); and (b) administering GSK2118436 for an additional 14 days, prior to administering treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake after 28 days of treatment).
- Safety and Tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]To evaluate the safety and tolerability, as determined by AE and SAE reporting, of GSK2118436 in combination with whole body iodine scans (all patients) and treatment doses of radioactive iodine (patients whose tumors demonstrate significant iodine uptake).
- Clinical Benefit [ Time Frame: 2 years ] [ Designated as safety issue: No ]To evaluate parameters of clinical benefit as measured by decreases in the serum tumor marker, thyroglobulin, and objective response rate per modified RECIST 1.1.
- Pharmacodynamic Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]To investigate the pharmacodynamic (PD) response to GSK2118436 as assessed in pre- and post-treatment circulating tumors cells (CTC—all patients) and fine needle aspirates (FNA) in consenting patients with accessible tumors by measuring: (i) phospho-ERK levels; (ii) sodium iodide symporter (NIS) levels; and (iii) the proliferation marker, Ki-67.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01534897
|Contact: Stephen M Rothenberg, MD, PhDfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator: Stephen M Rothenberg, MD, PhD|
|Principal Investigator:||Stephen M Rothenberg, MD, PhD||Massachusetts General Hospital|