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Follicular Thyroid CancerPhase 2NCT01723202

Dabrafenib With or Without Trametinib in Treating Patients With Advanced Differentiated Thyroid Cancer

A Phase 2 study testing dabrafenib and trametinib in people with Follicular Thyroid Cancer and Insular Thyroid Cancer, run by Bhavana Konda at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This randomized phase II trial studies how well dabrafenib works with or without trametinib in treating patients with recurrent thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
dabrafenib and trametinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
5 sitesUnited States
Study dates
7 Nov 2012to 15 Apr 2022
Phase
Phase 2
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

  • Patients must have histologically or cytologically confirmed papillary thyroid cancer, follicular thyroid cancer (tall cell variant, insular thyroid cancer, follicular variant of papillary thyroid cancers, poorly differentiated thyroid cancer or any of the above mixed histology will be allowed)
  • Presence of BRAF mutation in tumor tissue
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; malignant lymph nodes will be considered measurable if they are >= 15 mm in short axis
  • Patients must have progressive disease within the thirteen months prior to study entry; progressive disease is as defined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, which is at least a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5 mm; the appearance of one or more new lesions is also considered progressive disease
  • Patients are willing to have tumor biopsy pre-study and at 4 weeks on study (fine needle aspiration or core biopsy) if patient has biopsy-accessible tumors as determined by investigator
  • Patients must have disease that is refractory (unresponsive) to radioactive iodine (RAI) treatment as defined by one of the following:
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  • One or more measurable lesions that do not demonstrate RAI uptake
  • One or more measurable lesions progressive by RECIST 1.1 within 12-months of prior RAI therapy
  • Cumulative RAI dose of > 600 mCi
  • Prior therapy allowed:
  • Patients may have been previously treated with up to three regimens of oral multikinase inhibitors, including sorafenib, sunitinib and pazopanib
  • Patients may have been previously treated with external beam radiation or cytotoxic chemotherapy therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Serum creatinine =< 1.5 X institutional upper limit of normal
  • Left ventricular ejection fraction (EF) >= institutional lower limit of normal
  • Patient must have a calcium phosphate product (CPP) =< 4.0 mmol^2/L^2 (50 mg^2/dL^2)
  • Female patients of childbearing age are required to have a negative serum pregnancy test within 14 days prior to the first dose of study medication
  • Females are required to use an effective method of contraception from the time of negative serum pregnancy test, throughout the study duration, and until 4 weeks after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 16 weeks after completion of the last dose of study drug
  • Specific contraception requirements for females: female subjects of childbearing potential must not become pregnant and are required to be sexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%; sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject; periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception; contraceptive methods with a failure rate of < 1% include the following:
  • Intrauterine device (IUD) or intrauterine system (IUS) that meets the < 1% failure rate as stated in the product label
  • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is patient's sole sexual partner; for this definition, "documented" refers to the outcome of the investigator's/qualified physician designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records
  • Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); these allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label; the investigator is responsible for ensuring subjects understand how to properly use these methods of contraception
  • Specific contraception requirements for males: to prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject's semen, male subjects must use one of the following contraceptive methods during the study and for a total of 16 weeks following the last dose of study drug (based upon the lifecycle of sperm):
  • Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject for 14 days prior to first dose of study drug, through the dosing period, and for at least 16 weeks after the last dose of study drug; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Condom (during non-vaginal intercourse with any partner - male or female) OR
  • Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female)
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients had external beam radiotherapy, cytotoxic chemotherapy, or oral multikinase inhibitors within 4 weeks prior to entering the study
  • Patients who have been treated with radioactive iodine within 24 weeks prior to entering the study (radioactive iodine within 4 weeks will be allowed if negative post-treatment scan)
  • Patients have not recovered from adverse events related to prior chemotherapy, radiation therapy or multikinase inhibitors to Common Terminology Criteria for Adverse Events (CTCAE) 4.0 grade 1 or less except for alopecia
  • Patients have been previously treated with potent BRAF inhibitor or MEK inhibitor, including PLX4032/vemurafenib, ARQ 736; previous treatment with sorafenib is permitted
  • Patients are receiving any other investigational agents
  • Patients are on any medication that is on the list of prohibitive medications; patients on therapeutic dose of warfarin; this is due to potential for significant interactions between warfarin and study agents
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  • Patients with a known history of infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • Patients with a history of other malignancy; patients who have been disease-free from other malignancy for 5 years or greater, or patients with a history of resected non-melanoma skin cancer, or patients with a history of treated in situ carcinoma will be allowed
  • Patients with uncontrolled brain metastases; patients who are on a stable dose of corticosteroids for more than 1 month or off corticosteroids for 2 weeks can be enrolled; enzyme-inducing anti-epileptic drugs are not permitted
  • Patients with a known history of retinal vein occlusion or central serous retinopathy, or predisposing factors to retinal vein occlusion (RVO) or central serous retinopathy (CSR) (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
  • Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
  • Evidence of new optic disc cupping
  • Evidence of new visual field defects
  • Intraocular pressure > 21 mm Hg as measured by tonography
  • Patients with a known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Patients with class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
  • Abnormal cardiac valve morphology (subjects with minimal abnormalities, can be entered on study with approval)
  • Corrected QT (QTc) interval greater than or equal to 480 msecs (>= 500 msec for subjects with bundle branch block)
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women and nursing women are excluded from this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Subjects with a history of pneumonitis or interstitial lung disease
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months
  • History of uncontrolled arrhythmias; subjects with controlled atrial fibrillation for > 1 month prior to study day 1 are eligible

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Massachusetts General Hospital, Harvard Medical School

    Boston, Massachusetts, 02114

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • The University of Texas-MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California, San Diego

    San Diego, California, 92093-0698

Other trials in United States

About this study

Official title: A Randomized Phase 2 Study of Single Agent Dabrafenib (BRAFi) vs. Combination Regimen Dabrafenib (BRAFi) and Trametinib (MEKi) in Patients With BRAF Mutated Thyroid Carcinoma

This randomized phase II trial studies how well dabrafenib works with or without trametinib in treating patients with recurrent thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether dabrafenib is more effective when given with or without trametinib in treating thyroid cancer

Read the detailed description

PRIMARY OBJECTIVES:

  1. To screen two different regimens (GSK2118436 [BRAFi] [dabrafenib] as a single agent versus the combination regimen of GSK2118436 [BRAFi] and GSK1120212 [MEKi] [trametinib]) and identify which regimen is more promising for subsequent testing in a phase III trial in radioiodine refractory BRAF-mutated differentiated thyroid cancer (DTC) patients.

SECONDARY OBJECTIVES:

  1. To understand duration of objective response, progression-free survival and overall survival for each treatment group.

II. To assess tolerability and adverse events of GSK2118436 (BRAFi) as a single agent and the tolerability and adverse events of GSK2118436 (BRAFi) and GSK1120212 (MEKi) in combination, in patients with DTC.

III. To evaluate impact of experimental drugs on serum tumor marker thyroglobulin and its correlation with overall response rate.

IV. To understand pharmacokinetic, pharmacogenetics and pharmacodynamics of experimental drugs using serial tumor biopsies, tumor blocks and peripheral blood.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive dabrafenib orally (PO) twice daily (BID) on days 1-28. Patients with disease progression may cross-over to arm II.

ARM II: Patients receive dabrafenib PO BID and trametinib PO once daily (QD) on days 1-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks.

Being tested
dabrafenib, trametinib
Keywords
BRAF, BRAFi, thyroid cancer, thyroid carcinoma
Medical subject headings
Adenocarcinoma, Follicular, Thyroid Cancer, Papillary, Thyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dabrafenibDrug

    Also called BRAF inhibitor GSK2118436, GSK2118436

    150 mg orally twice daily given orally

  • trametinibDrug

    Also called GSK1120212, MEKi

    150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally

Study groups in NCT01723202
Study groupRoleWhat they receive
Arm A: GSK2118436ExperimentalPatients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II.
Receives: Drug: dabrafenib
Arm B: GSK2118436 and GSK1120212ExperimentalPatients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28.
Receives: Drug: dabrafenib; Drug: trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Objective Response Rate, Defined as the Proportion of Patients Who Have a Minor Response (MR), Partial Response (PR), or Complete Response(CR)Assessed According to RECIST.

    The MR+PR+CR response rate will be estimated for each treatment arm. In determining this rate, the number of patients with RECIST-based MR, PR or CR will be divided by the number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.

    Measured: up to 24 weeks

Secondary outcomes (4)

  1. Progression-free Survival (PFS)

    The MR+PR+CR response rate will be estimated for each treatment arm. In determining this rate, the number of patients with RECIST-based MR, PR or CR will be divided by the number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true PR+CR response rate

    Measured: Up to 4 years or from start of treatment to time of progression or death

  2. Overall Survival

    The Kaplan-Meier method will be used to estimate overall survival. We will also evaluate the proportion of patients who are alive at one year.

    Measured: up to 4 weeks after study treatment

  3. Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination.

    Frequency and severity of adverse events in each of the treatment arms will be collected and summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described.

    Measured: Every 2 weeks for the first 8 weeks, and then every 4-8 weeks thereafter up to 4 weeks after completion of study treatment, up to 1 year

  4. Tolerability of the Regimens in Terms of the Number of Patients Who Required Dose Modifications and/or Dose Delays.

    Tolerability of the regimen in each of the treatment arms will be collected and summarized using descriptive statistics. We will also capture the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial. These tolerability measures will be assessed within each of the treatment arms and we will explore differences in these measures between the arms.

    Measured: Every 2 weeks for the first 8 weeks, and then every 4-8 weeks thereafter up to 4 weeks after completion of study treatment, up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2012 (estimated)
  2. Study start7 Nov 2012
  3. Primary completion15 Apr 2022
  4. Study completion15 Apr 2022

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01723202
Sponsor's protocol ID
OSU-12064
Other IDs
NCI-2012-01700, NCCNGSK20008
Status last verified
Aug 2025
First submitted
22 Oct 2012
Last updated
24 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Busaidy NL, Konda B, Wei L, Wirth LJ, Devine C, Daniels GA, DeSouza JA, Poi M, Seligson ND, Cabanillas ME, Sipos JA, Ringel MD, Eisfeld AK, Timmers C, Shah MH. Dabrafenib Versus Dabrafenib + Trametinib in BRAF-Mutated Radioactive Iodine Refractory Differentiated Thyroid Cancer: Results of a Randomized, Phase 2, Open-Label Multicenter Trial. Thyroid. 2022 Oct;32(10):1184-1192. doi: 10.1089/thy.2022.0115. Epub 2022 Jul 5.

    PubMed 35658604

  • Hicks HM, Pozdeyev N, Sams SB, Pugazhenthi U, Bales ES, Hofmann MC, McKenna LR, Schweppe RE. Fibronectin Contributes to a BRAF Inhibitor-driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2. Mol Cancer Res. 2023 Sep 1;21(9):867-880. doi: 10.1158/1541-7786.MCR-22-1031.

    PubMed 37219859

  • Owen DH, Konda B, Sipos J, Liu T, Webb A, Ringel MD, Timmers CD, Shah MH. KRAS G12V Mutation in Acquired Resistance to Combined BRAF and MEK Inhibition in Papillary Thyroid Cancer. J Natl Compr Canc Netw. 2019 May 1;17(5):409-413. doi: 10.6004/jnccn.2019.7292.

    PubMed 31085763

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing dabrafenib and trametinib in people with Follicular Thyroid Cancer and Insular Thyroid Cancer, run by Bhavana Konda at 5 sites 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 31 inclusion and 24 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 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2025). 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?

Overall Objective Response Rate, Defined as the Proportion of Patients Who Have a Minor Response (MR), Partial Response (PR), or Complete Response(CR)Assessed According to RECIST. (time frame: up to 24 weeks). 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 NCT01723202, which also lists 3 linked publications.

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 24 Aug 2025.

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