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

NCT01723202 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: OSU-12064NCI-2012-01700NCCNGSK20008
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 5

Brief 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. It is not yet known whether dabrafenib is more effective when given with or without trametinib in treating thyroid cancer

Conditions

Follicular Thyroid Cancer; Insular Thyroid Cancer; Papillary Thyroid Cancer; Recurrent Thyroid Cancer

Keywords

BRAF; BRAFi; thyroid cancer; thyroid carcinoma

Outcome Measures

Primary Outcomes (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.

  up to 24 weeks

Secondary Outcomes (4)

• Progression-free Survival (PFS)

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

• Overall Survival

  up to 4 weeks after study treatment

• 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.

  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

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

  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

Study Arms (2)

Arm A: GSK2118436

EXPERIMENTAL

Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II.

Drug: dabrafenib

Arm B: GSK2118436 and GSK1120212

EXPERIMENTAL

Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28.

Drug: dabrafenib; Drug: trametinib

Interventions

dabrafenib DRUG

150 mg orally twice daily given orally

Also known as: BRAF inhibitor GSK2118436, GSK2118436

Arm A: GSK2118436; Arm B: GSK2118436 and GSK1120212

trametinib DRUG

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

Also known as: GSK1120212, MEKi

Arm B: GSK2118436 and GSK1120212

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bhavana Konda: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (5)

University of California, San Diego

San Diego, California, 92093-0698, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital, Harvard Medical School

Boston, Massachusetts, 02114, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

The University of Texas-MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• 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.

  PMID: 35658604 RESULT

• 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.

  PMID: 37219859 DERIVED

• 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.

  PMID: 31085763 DERIVED

Related Links

• Jamesline

MeSH Terms

Conditions

Adenocarcinoma, Follicular; Thyroid Cancer, Papillary; Thyroid Neoplasms

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma, Papillary; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Dr. Bhavana Konda
• Organization: The Ohio State University Comprehensive Cancer Center

Bhvana.konda@osumc.edu

614-366-5068

Study Officials

• Bhavana Konda, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: November 7, 2012
• Study Start: November 7, 2012
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: August 24, 2025
• Results First Posted: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)