Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436

• Status: Completed
• Trial end date: 2014-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborator: GlaxoSmithKline
• Treatments: Dabrafenib

Criteria

Inclusion Criteria:

• Histologically confirmed papillary thyroid carcinoma, including its variants, such as tall cell PTC or poorly differentiated thyroid carcinoma, that is metastatic or unresectable AND harbors a BRAF V600E mutation

• Evaluable disease, as defined by at least one lesion that can be accurately measured in at least one dimension on CT scan or ultrasound, if present in the neck

• Radioiodine-refractory disease

• Life expectancy > 6 months

• Able to swallow and retain oral medication

• Normal organ and marrow function

Exclusion Criteria:

• Pregnant or breastfeeding

• Previous treatment with a specific BRAF or MEK inhibitor

• Receiving any other study agents

• Known brain metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GSK2118436, bovine TSH, mannitol or iodine

• Active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs

• History of known glucose-6-phosphate dehyrogenase (G6PD) deficiency

• Corrected QT interval >/= 480 msecs; history of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks; Class II, III, or IV heart failure, abnormal cardiac valve morphology; or history of known cardiac arrhythmias

• Taking herbal remedies

• Subjects with significant symptoms from their thyroid cancer, or have a large burden of rapidly progressive iodine-refractory PTC who are in need of other systemic therapy, as judged by their treating physician

• Uncontrolled current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements

• History of a different malignancy unless disease-free for at least 5 years and deemed to be at low risk for recurrence

• HIV-positive on combination antiretroviral therapy