Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer
A Randomized Phase III Study of BRAF-Targeted Therapy vs Cabozantinib in RAI-Refractory Differentiated Thyroid Cancer With BRAF V600Em
3 other identifiers
interventional
264
1 country
112
Brief Summary
This phase III trial compares the effect of cabozantinib versus combination dabrafenib and trametinib for the treatment of patients with differentiated thyroid cancer that does not respond to treatment (refractory) and which expresses a BRAF V600E mutation. Cabozantinib is in a class of medications called receptor tyrosine kinase inhibitors. It binds to and blocks the action of several enzymes which are often over-expressed in a variety of tumor cell types. This may help stop or slow the growth of tumor cells and blood vessels the tumor needs to survive. Dabrafenib is an enzyme inhibitor that binds to and inhibits the activity of a protein called B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. Trametinib is also an enzyme inhibitor. It binds to and inhibits the activity of proteins called MEK 1 and 2, which play a key role in activating pathways that regulate cell growth. This may inhibit the growth of tumor cells mediated by these pathways. The usual approach for patients with thyroid cancer is targeted therapy with dabrafenib and trametinib. This trial may help researchers decide which treatment option (cabozantinib alone or dabrafenib in combination with trametinib) is safer and/or more effective in treating patients with refractory BRAF V600E-mutated differentiated thyroid cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2024
Longer than P75 for phase_3
112 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 17, 2024
CompletedFirst Posted
Study publicly available on registry
June 26, 2024
CompletedStudy Start
First participant enrolled
August 22, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2030
May 5, 2026
April 1, 2026
6.1 years
May 17, 2024
April 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
PFS will be compared between the two groups using a stratified log-rank test with one-sided type I error of 0.05. Median PFS and 95% confidence interval (CI) for each treatment arm will be estimated using the Kaplan-Meier method. The stratified hazard ratio and 95% CI will be estimated using a Cox proportional hazard model with treatment group as the independent variable.
From randomization to radiographic progression of disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, up to 5 years
Secondary Outcomes (5)
Objective response
Up to 5 years
Overall survival
From randomization to death from any cause, up to 5 years
Duration of response
From confirmed response (complete response or partial response) to progression among patients who achieve a response, up to 5 years
PFS2 - the time from randomization to progression on subsequent therapy or death from any cause (whichever occurs first)
From randomization to progression on subsequent therapy or death from any cause, up to 5 years
Incidence of adverse events
at 2 weeks, 4 weeks, 8 weeks, 16 weeks, and then every 12 weeks after the 16-week confirmatory scan
Other Outcomes (1)
Patient tolerability
At baseline, 4, 8, 16, and 28 weeks
Study Arms (2)
Arm A (Dabrafenib and trametinib)
ACTIVE COMPARATORPatients receive dabrafenib PO BID and trametinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, blood sample collection and may undergo MRI throughout the study.
Arm B (Cabozantinib)
EXPERIMENTALPatients receive cabozantinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, blood sample collection and may undergo MRI throughout the study.
Interventions
Undergo blood sample collection
Undergo CT scan
Given PO
Undergo MRI
Ancillary study
Given PO
Eligibility Criteria
You may qualify if:
- Patient must be ≥ 18 years of age
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patient must have differentiated thyroid cancer (DTC) with BRAF V600E mutation as determined by local testing, including the following subtypes (Note: results of a previous biopsy will be accepted):
- Papillary thyroid carcinoma including histological variants of papillary thyroid carcinoma (PTC) such as follicular variant, tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin-like, trabecular, tumor with nodular fasciitis-like stroma, HĂ¼rthle cell variant of papillary carcinoma, poorly differentiated.
- Follicular thyroid carcinoma including histological variants of follicular thyroid carcinoma (FTC) such as HĂ¼rthle cell, clear cell, insular, and poorly differentiated
- Patient must have been previously treated with or deemed ineligible for treatment with Iodine-131 for DTC, and must be receiving thyroxine suppression therapy
- Patient must have had prior treatment with at least one of the following vascular endothelial growth factor receptors (VEGFR)-targeting tyrosine kinase inhibitor (TKI) agents for DTC: lenvatinib or sorafenib.
- NOTE: Up to two prior VEGFR-targeting TKI agents are allowed including, but not limited to lenvatinib and sorafenib
- Patient must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1·1 on chest CT (computed tomography)/abdominal/pelvis CT/MRI (magnetic resonance imaging) performed within 4 weeks prior to randomization
- Patient must have radiographic progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 over any time interval on or after most recent prior systemic treatment
- Patient must not have any of the following cardiovascular and thromboembolic disorders or medical conditions:
- Congestive heart failure class 3 or 4 as defined by the New York Heart Association, unstable angina pectoris, or serious cardiac arrhythmias.
- Uncontrolled hypertension defined as sustained blood pressure \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
- Stroke, myocardial infarction, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months prior to randomization. Patients with more recent diagnosis of deep venous thrombosis are allowed if stable and treated with therapeutic anticoagulation for at least 6 weeks prior to randomization
- Patient must not have any clinically significant hematemesis or haemoptysis of \> 0·5 teaspoon (\> 2·5 mL) of red blood or history of other significant bleeding within 3 months prior to randomization
- +34 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)collaborator
- ECOG-ACRIN Cancer Research Grouplead
Study Sites (112)
Mercy Hospital Fort Smith
Fort Smith, Arkansas, 72903, United States
CARTI Cancer Center
Little Rock, Arkansas, 72205, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, 06033, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, 06902, United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Walter Knox Memorial Hospital
Emmett, Idaho, 83617, United States
Idaho Urologic Institute-Meridian
Meridian, Idaho, 83642, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
OSF Saint Anthony's Health Center
Alton, Illinois, 62002, United States
Saint Mary's Hospital
Centralia, Illinois, 62801, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois
Chicago, Illinois, 60612, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Good Samaritan Regional Health Center
Mount Vernon, Illinois, 62864, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Mercy Hospital
Cedar Rapids, Iowa, 52403, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403, United States
Central Care Cancer Center - Garden City
Garden City, Kansas, 67846, United States
Central Care Cancer Center - Great Bend
Great Bend, Kansas, 67530, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337, United States
Cambridge Medical Center
Cambridge, Minnesota, 55008, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Fairview Clinics and Surgery Center Maple Grove
Maple Grove, Minnesota, 55369, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
Health Partners Inc
Minneapolis, Minnesota, 55454, United States
Monticello Cancer Center
Monticello, Minnesota, 55362, United States
New Ulm Medical Center
New Ulm, Minnesota, 56073, United States
Fairview Northland Medical Center
Princeton, Minnesota, 55371, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379, United States
Lakeview Hospital
Stillwater, Minnesota, 55082, United States
Sanford Thief River Falls Medical Center
Thief River Falls, Minnesota, 56701, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Sanford Cancer Center Worthington
Worthington, Minnesota, 56187, United States
Fairview Lakes Medical Center
Wyoming, Minnesota, 55092, United States
Saint Louis Cancer and Breast Institute-Ballwin
Ballwin, Missouri, 63011, United States
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613, United States
Cox Cancer Center Branson
Branson, Missouri, 65616, United States
Southeast Cancer Center
Cape Girardeau, Missouri, 63703, United States
Freeman Health System
Joplin, Missouri, 64804, United States
Mercy Hospital Joplin
Joplin, Missouri, 64804, United States
Lake Regional Hospital
Osage Beach, Missouri, 65065, United States
Delbert Day Cancer Institute at PCRMC
Rolla, Missouri, 65401, United States
Mercy Clinic-Rolla-Cancer and Hematology
Rolla, Missouri, 65401, United States
Heartland Regional Medical Center
Saint Joseph, Missouri, 64506, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
CoxHealth South Hospital
Springfield, Missouri, 65807, United States
Saint Louis Cancer and Breast Institute-South City
St Louis, Missouri, 63109, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Mercy Hospital Washington
Washington, Missouri, 63090, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Great Falls Clinic
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Sanford South University Medical Center
Fargo, North Dakota, 58103, United States
Southpointe-Sanford Medical Center Fargo
Fargo, North Dakota, 58103, United States
Sanford Medical Center Fargo
Fargo, North Dakota, 58104, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Mercy Hospital Oklahoma City
Oklahoma City, Oklahoma, 73120, United States
Saint Alphonsus Cancer Care Center-Baker City
Baker City, Oregon, 97814, United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Smilow Cancer Hospital Care Center - Westerly
Westerly, Rhode Island, 02891, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
Billings Clinic-Cody
Cody, Wyoming, 82414, United States
Welch Cancer Center
Sheridan, Wyoming, 82801, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lova Sun
ECOG-ACRIN Cancer Research Group
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 17, 2024
First Posted
June 26, 2024
Study Start
August 22, 2024
Primary Completion (Estimated)
September 30, 2030
Study Completion (Estimated)
September 30, 2030
Last Updated
May 5, 2026
Record last verified: 2026-04