Papillary Thyroid CarcinomaNCT01534897
Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436
A study testing GSK2118436 in people with Papillary Thyroid Carcinoma, run by Massachusetts General Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Papillary Thyroid Carcinoma
- What is being tested?
- GSK2118436
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Mar 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02215
About this study
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.
Read the detailed description
You will take GSK2118436 capsules by mouth for 28 straight days. If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will take GSK2118436 for an additional 14 days (Days 29-42). You will be given a drug diary to record when you take GSK2118436. This diary will also contain instructions on how to take GSK2118436.
Prior to Day 1
- Optional fine needle aspirate (pre-treatment) Day 1
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for Circulating Tumor Cells (CTCs). (4 teaspoons of blood)
- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436
Day 2:
- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436 Day 3-5: Research blood sample for CTCs Days 8 and 15
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- Optional fine needle aspirate (Day 15 only) Low Iodine Diet: You will begin a low iodine diet on Day 15, in preparation for Day 23 when you will receive radioactive iodine (131I). The study team will provide you with instructions on this diet. The low iodine diet will be continued until the whole body scan is complete. For those participants who will receive a therapeutic dose of radioactive iodine on Day 37, the low iodine diet will be continued until the Day 42 whole body scan is complete.
Days 21 and 22: The drug thyrogen will be administered as in injection into your buttocks on Days 21 and 22 in preparation for your whole body radioactive iodine scan on Day 28. Thyrogen is used as a diagnostic tool to help determine the status of your cancer and is approved for use in thyroid cancer patients.
Day 23: To prepare for the whole body radioactive iodine scan, you will be asked to swallow a capsule of radioactive iodine which will be absorbed by any remaining thyroid cells in your body. Radioactive iodine is approved for use in thyroid cancer patients. You will then be asked to return for the scan on Day 28.You will be asked to sign a separate consent for the radioactive iodine.
Days 1-28:
- Optional repeat fine needle aspirate Day 28
- Whole body radioactive iodine scan to assess your thyroid cancer
If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will have the following tests done within 24 hours:
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- An injection of a therapeutic dose of radioactive iodine will be administered. If your Day 28 whole body radioactive iodine scan does not demonstrate significant uptake of iodine, you will be removed from the research study. You will have a 3 month follow up appointment as outlined below.
If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will continue treatment with GSK2118436 and have the following study visits:
Days 35 and 36: The drug thyrogen will be administered as in injection into your buttocks on Days 35 and 36 in preparation for your whole body radioactive iodine scan on Day 42.
Day 37: You will be given a therapeutic dose of radioactive iodine. You will be given a separate consent form to sign for your radioactive iodine treatment. You will then be asked to return for the whole body radioactive iodine scan on Day 42.
Day 39:
- Vital signs
- Routine blood tests (1 tablespoon)
Day 42:
- Whole body radioactive iodine scan
- Research blood sample for CTCs. (4 teaspoons of blood)
After the final dose of the study drug: All participants will have a follow up visit 3 months after you stop the study drug. You will have the following tests at this visit:
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- An assessment of your tumor by CT scan or PET/CT scan of your neck, chest, abdomen and pelvis.
- Those participants who had a therapeutic dose of radioactive iodine on Day 37 will have a whole body radioactive iodine scan.
- Optional fine needle aspirate
- Conditions
- Papillary Thyroid Carcinoma
- Being tested
- GSK2118436
- Keywords
- thyroid cancer, Tall cell PTC, Poorly differentiated thyroid carcinoma, metastatic
- Medical subject headings
- Thyroid Cancer, Papillary, Thyroid Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2118436Drug
Also called Dabrafenib
150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: GSK2118436 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 25 days after start of Dabrafenib (GSK2118436)
Secondary outcomes (4)
Safety Analysis as Number of Participants With Adverse Events
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).
Measured: 2 years
Clinical Benefit as Measured by Change in Tumor Size
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).
Measured: 2 years
Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions
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).
Measured: 2 years
Clinical Benefit as Measured by Change in Thyroglobulin Level
To evaluate clinical benefit as measured by change in serum tumor marker, thyroglobulin. Rising thyroglobulin is generally indicative of tumor growth.
Measured: 3 months after radioiodine therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2012 (estimated)
- Study startJul 2012
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Papillary Thyroid CarcinomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Lori J. Wirth, MD, Massachusetts General Hospital
- Investigators
- Stephen M Rothenberg, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01534897
- Sponsor's protocol ID
- 11-337
- Status last verified
- Jan 2017
- First submitted
- 10 Feb 2012
- Last updated
- 15 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25549723
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436
- ClinicalTrials.gov ID
- NCT01534897
- Acronym / sponsor ID
- 11-337
- Conditions
- Papillary Thyroid Carcinoma
- Keywords
- thyroid cancer, Tall cell PTC, Poorly differentiated thyroid carcinoma, metastatic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jul 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 17 Feb 2012 (estimated)
- Results
- Posted 15 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
You will take GSK2118436 capsules by mouth for 28 straight days. If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will take GSK2118436 for an additional 14 days (Days 29-42). You will be given a drug diary to record when you take GSK2118436. This diary will also contain instructions on how to take GSK2118436.
Prior to Day 1
- Optional fine needle aspirate (pre-treatment) Day 1
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for Circulating Tumor Cells (CTCs). (4 teaspoons of blood)
- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436
Day 2:
- Optional research blood sample for CTCs 4-6 hours after the first dose of GSK2118436 Day 3-5: Research blood sample for CTCs Days 8 and 15
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- Optional fine needle aspirate (Day 15 only) Low Iodine Diet: You will begin a low iodine diet on Day 15, in preparation for Day 23 when you will receive radioactive iodine (131I). The study team will provide you with instructions on this diet. The low iodine diet will be continued until the whole body scan is complete. For those participants who will receive a therapeutic dose of radioactive iodine on Day 37, the low iodine diet will be continued until the Day 42 whole body scan is complete.
Days 21 and 22: The drug thyrogen will be administered as in injection into your buttocks on Days 21 and 22 in preparation for your whole body radioactive iodine scan on Day 28. Thyrogen is used as a diagnostic tool to help determine the status of your cancer and is approved for use in thyroid cancer patients.
Day 23: To prepare for the whole body radioactive iodine scan, you will be asked to swallow a capsule of radioactive iodine which will be absorbed by any remaining thyroid cells in your body. Radioactive iodine is approved for use in thyroid cancer patients. You will then be asked to return for the scan on Day 28.You will be asked to sign a separate consent for the radioactive iodine.
Days 1-28:
- Optional repeat fine needle aspirate Day 28
- Whole body radioactive iodine scan to assess your thyroid cancer
If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will have the following tests done within 24 hours:
- Vital signs
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- An injection of a therapeutic dose of radioactive iodine will be administered. If your Day 28 whole body radioactive iodine scan does not demonstrate significant uptake of iodine, you will be removed from the research study. You will have a 3 month follow up appointment as outlined below.
If your Day 28 whole body radioactive iodine scan demonstrates significant uptake of iodine, you will continue treatment with GSK2118436 and have the following study visits:
Days 35 and 36: The drug thyrogen will be administered as in injection into your buttocks on Days 35 and 36 in preparation for your whole body radioactive iodine scan on Day 42.
Day 37: You will be given a therapeutic dose of radioactive iodine. You will be given a separate consent form to sign for your radioactive iodine treatment. You will then be asked to return for the whole body radioactive iodine scan on Day 42.
Day 39:
- Vital signs
- Routine blood tests (1 tablespoon)
Day 42:
- Whole body radioactive iodine scan
- Research blood sample for CTCs. (4 teaspoons of blood)
After the final dose of the study drug: All participants will have a follow up visit 3 months after you stop the study drug. You will have the following tests at this visit:
- Routine blood tests (2 tablespoons)
- Research blood sample for CTCs. (4 teaspoons of blood)
- An assessment of your tumor by CT scan or PET/CT scan of your neck, chest, abdomen and pelvis.
- Those participants who had a therapeutic dose of radioactive iodine on Day 37 will have a whole body radioactive iodine scan.
- Optional fine needle aspirate
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2118436 | Experimental | Drug: GSK2118436Intervention: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2118436Also: Dabrafenib150mg twice per day orally for 28 days (42 days if Iodine-131 scan on Day 25 shows new uptake) | Drug | GSK2118436 |
Primary outcome
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.
4 secondary outcomes
Safety Analysis as Number of Participants With Adverse Events
Time frame: 2 years
Clinical Benefit as Measured by Change in Tumor Size
Time frame: 2 years
Number of Participants Who Complete the Study With Minimal Delays and no Dose Reductions
Time frame: 2 years
Clinical Benefit as Measured by Change in Thyroglobulin Level
Time frame: 3 months after radioiodine therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25549723Rothenberg 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.
- pubmed url for articleLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen M Rothenberg, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GSK2118436 in people with Papillary Thyroid Carcinoma, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Increased Radioiodine Uptake (time frame: 25 days after start of Dabrafenib (GSK2118436)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01534897, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2017.