Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436
|ClinicalTrials.gov Identifier: NCT01534897|
Recruitment Status : Completed
First Posted : February 17, 2012
Results First Posted : March 15, 2017
Last Update Posted : March 15, 2017
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.
|Condition or disease||Intervention/treatment|
|Papillary Thyroid Carcinoma||Drug: GSK2118436|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436|
|Study Start Date :||July 2012|
|Primary Completion Date :||March 2014|
|Study Completion Date :||March 2014|
Intervention: GSK2118436 (dabrafenib) 150mg by mouth twice per day for 28 days, continued to day 42 if the Day 25 Iodine-131 scan shows new uptake. Patients with new Iodine-131 uptake on Day 25 who continue dabrafenib to day 42 receive a treatment dose (150 mCi) of Iodine-131 on Day 37.
150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)
Other Name: Dabrafenib
- Increased Radioiodine Uptake [ Time Frame: 25 days after start of Dabrafenib (GSK2118436) ]Number of patients with radioiodine-refractory metastatic BRAF V600E-mutant PTC who have increased radioiodine uptake in their disease sites while on dabrafenib. Radioiodine uptake is assessed by whole body scan and areas of interest are identified by nuclear medicine physicians.
- Safety Analysis as Number of Participants With Adverse Events [ Time Frame: 2 years ]To evaluate the safety and tolerability, as determined by adverse event and serious adverse event 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 as Measured by Change in Tumor Size [ Time Frame: 2 years ]To evaluate clinical benefit as measured by objective response rate per modified RECIST 1.1, which assesses changes in size of measurable tumors. (per RECIST, a partial response (PR) = at least 30% decrease in size of tumor; progressive disease (PD) = at least 20% increase in size of tumor; stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).
- Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions [ Time Frame: 2 years ]To determine the feasibility 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).
- Clinical Benefit as Measured by Change in Thyroglobulin Level [ Time Frame: 3 months after radioiodine therapy ]To evaluate clinical benefit as measured by change in serum tumor marker, thyroglobulin. Rising thyroglobulin is generally indicative of tumor growth.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01534897
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Stephen M Rothenberg, MD, PhD||Massachusetts General Hospital|