Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer

Recruiting now · Phase 3

Conditions studied: Refractory Differentiated Thyroid Gland Carcinoma

In brief

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.

Key facts

Study ID

NCT06475989

Run by

ECOG-ACRIN Cancer Research Group

People needed

264

Starts

2024-08-22

Expected to finish

2030-09-30

Last updated by the study team

2026-08-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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, Hürthle cell variant of papillary carcinoma, poorly differentiated.
• Follicular thyroid carcinoma including histological variants of follicular thyroid carcinoma (FTC) such as Hürthle 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
• Patient must not have any cavitating pulmonary lesion(s) or lesions invading major pulmonary blood vessels
• Patient must not be on any concomitant anticoagulation with oral anticoagulants or platelet inhibitors, except for the following allowed agents:
• Low-dose aspirin for cardioprotection.
• Therapeutic anticoagulation with any agent in patients (1) without known brain metastases, (2) on a stable dose for at least 6 weeks prior to randomization, and (3) with no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• Patient must not have any gastrointestinal (GI) disorders associated with a high risk of perforation or fistula formation:
• Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months prior to randomization
• Patient must have completed any prior local therapy (e.g., surgery, radiation, ablation) at least 4 weeks prior to randomization, with complete wound healing and resolution of clinically relevant complications from prior local therapy
• Patient must not have had major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Complete wound healing from major surgery must have occurred 4 weeks prior to randomization and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days prior to randomization
• Patient must not have any lesion(s) with ≥ 2cm growth within 3 months or ≥ 1.5cm growth within 2 months prior to randomization, and must not have documented anaplastic histology at or following cancer recurrence

Where it is running

• Anchorage Associates in Radiation Medicine — Anchorage, Alaska, United States (enrolling)
• Smilow Cancer Hospital Care Center at Saint Francis — Hartford, Connecticut, United States (enrolling)
• Alaska Breast Care and Surgery LLC — Anchorage, Alaska, United States (enrolling)
• Alaska Oncology and Hematology LLC — Anchorage, Alaska, United States (enrolling)
• Alaska Women's Cancer Care — Anchorage, Alaska, United States (enrolling)
• Katmai Oncology Group — Anchorage, Alaska, United States (enrolling)
• Providence Alaska Medical Center — Anchorage, Alaska, United States (enrolling)
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States (enrolling)
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States (enrolling)
• CARTI Cancer Center — Little Rock, Arkansas, United States (enrolling)
• Providence Saint Joseph Medical Center/Disney Family Cancer Center — Burbank, California, United States (enrolling)
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States (enrolling)
• Providence Queen of The Valley — Napa, California, United States (enrolling)
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States (enrolling)
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States (enrolling)
• Providence Medical Foundation - Santa Rosa — Santa Rosa, California, United States (enrolling)
• Providence Santa Rosa Memorial Hospital — Santa Rosa, California, United States (enrolling)
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States (enrolling)
• UCHealth Highlands Ranch Hospital — Highlands Ranch, Colorado, United States (enrolling)
• Smilow Cancer Hospital-Derby Care Center — Derby, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center-Fairfield — Fairfield, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center at Glastonbury — Glastonbury, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center at Greenwich — Greenwich, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center - Guilford — Guilford, Connecticut, United States (enrolling)
• OSF Saint Anthony's Health Center — Alton, Illinois, United States (enrolling)

Full record on ClinicalTrials.gov

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