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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Lori J. Wirth, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01534897
First received: February 10, 2012
Last updated: January 24, 2017
Last verified: January 2017
  Purpose

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 Intervention
Papillary Thyroid Carcinoma
Drug: GSK2118436

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 10
Study Start Date: July 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2118436
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.
Drug: GSK2118436
150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)
Other Name: Dabrafenib

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534897

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
GlaxoSmithKline
Investigators
Principal Investigator: Stephen M Rothenberg, MD, PhD Massachusetts General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Lori J. Wirth, MD, Attending Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01534897     History of Changes
Other Study ID Numbers: 11-337
Study First Received: February 10, 2012
Results First Received: June 23, 2015
Last Updated: January 24, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Massachusetts General Hospital:
thyroid cancer
Tall cell PTC
Poorly differentiated thyroid carcinoma
metastatic

Additional relevant MeSH terms:
Carcinoma
Thyroid Diseases
Thyroid Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2017