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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2012 by Massachusetts General Hospital
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Stephen Rothenberg, M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01534897
First received: February 10, 2012
Last updated: August 2, 2012
Last verified: August 2012
  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: 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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 10
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)
Intervention Details:
    Drug: GSK2118436
    150mg twice per day orally for 28 days
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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

Contacts
Contact: Stephen M Rothenberg, MD, PhD 617-724-400 smrothenberg@partners.org

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

No publications provided

Responsible Party: Stephen Rothenberg, M.D., Prinicpal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01534897     History of Changes
Other Study ID Numbers: 11-337
Study First Received: February 10, 2012
Last Updated: August 2, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma
Thyroid Neoplasms
Thyroid Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 26, 2014