NCT01534897

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jul 2012

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 17, 2012

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
3 years until next milestone

Results Posted

Study results publicly available

March 15, 2017

Completed
Last Updated

March 15, 2017

Status Verified

January 1, 2017

Enrollment Period

1.7 years

First QC Date

February 10, 2012

Results QC Date

June 23, 2015

Last Update Submit

January 24, 2017

Conditions

Papillary Thyroid Carcinoma

Keywords

thyroid cancerTall cell PTCPoorly differentiated thyroid carcinomametastatic

Outcome Measures

Primary Outcomes (1)

  • Increased Radioiodine Uptake

    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.

    25 days after start of Dabrafenib (GSK2118436)

Secondary Outcomes (4)

  • Safety Analysis as Number of Participants With Adverse Events

    2 years

  • Clinical Benefit as Measured by Change in Tumor Size

    2 years

  • Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions

    2 years

  • Clinical Benefit as Measured by Change in Thyroglobulin Level

    3 months after radioiodine therapy

Study Arms (1)

GSK2118436

EXPERIMENTAL

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

Interventions

GSK2118436DRUG

150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)

Also known as: Dabrafenib
GSK2118436

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

  • Rothenberg SM, McFadden DG, Palmer EL, Daniels GH, Wirth LJ. Redifferentiation of iodine-refractory BRAF V600E-mutant metastatic papillary thyroid cancer with dabrafenib. Clin Cancer Res. 2015 Mar 1;21(5):1028-35. doi: 10.1158/1078-0432.CCR-14-2915. Epub 2014 Dec 30.

    PMID: 25549723RESULT

Related Links

MeSH Terms

Conditions

Thyroid Cancer, PapillaryThyroid NeoplasmsNeoplasm Metastasis

Interventions

dabrafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma, PapillaryAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteHead and Neck NeoplasmsEndocrine System DiseasesThyroid DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Dr. Lori J. Wirth
Organization
Massachusetts General Hospital Cancer Center
lwirth@mgh.harvard.edu
617 724 4000

Study Officials

  • Stephen M Rothenberg, MD, PhD

    Massachusetts General Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Attending Physician

Study Record Dates

First Submitted

February 10, 2012

First Posted

February 17, 2012

Study Start

July 1, 2012

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

March 15, 2017

Results First Posted

March 15, 2017

Record last verified: 2017-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)