Actively Recruiting

Phase 3
Age: 18Years +
All Genders
NCT06475989

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

Led by ECOG-ACRIN Cancer Research Group · Updated on 2026-05-05

264

Participants Needed

112

Research Sites

318 weeks

Total Duration

On this page

Sponsors

E

ECOG-ACRIN Cancer Research Group

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patient must be 18 years of age or older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Differentiated thyroid cancer with BRAF V600E mutation confirmed by local testing
  • Previously treated with or ineligible for Iodine-131 therapy and receiving thyroxine suppression
  • Prior treatment with at least one VEGFR-targeting tyrosine kinase inhibitor such as lenvatinib or sorafenib
  • Measurable disease by RECIST 1.1 on imaging within 4 weeks before randomization
  • Radiographic disease progression after most recent systemic treatment
  • No serious cardiovascular or thromboembolic conditions as specified
  • No clinically significant bleeding or cavitating pulmonary lesions
  • Not using oral anticoagulants or platelet inhibitors except allowed low-dose aspirin or stable therapeutic anticoagulation
  • No high-risk gastrointestinal disorders or recent abdominal complications
  • Completed prior local therapy at least 4 weeks before randomization with healed wounds
  • No major surgery within 8 weeks prior to randomization with healed wounds
  • No lesions with rapid growth or documented anaplastic histology at recurrence
  • No prior treatment with cabozantinib or BRAF-targeted therapy for thyroid cancer
  • Not pregnant or breastfeeding; use effective contraception if of childbearing potential
  • Ability to understand and sign informed consent
  • Adequate blood counts and organ function within 28 days prior to randomization
  • HIV patients with undetectable viral load on therapy eligible
  • Hepatitis B patients with undetectable viral load on therapy eligible
  • Hepatitis C patients treated and cured or with undetectable viral load if on treatment
  • Stable treated brain metastases with no progression for at least 4 weeks
  • Prior or concurrent malignancies allowed if not interfering with study
  • Corrected QT interval (QTcF) ≤ 500 ms within 28 days prior to randomization
  • English or Spanish speaking for quality of life assessment
Not Eligible

You will not qualify if you...

  • Congestive heart failure class 3 or 4, unstable angina, or serious cardiac arrhythmias
  • Uncontrolled hypertension despite treatment
  • Stroke, heart attack, or thromboembolic event within 6 months prior to randomization unless stable
  • Clinically significant hematemesis or hemoptysis within 3 months prior to randomization
  • Cavitating pulmonary lesions or lesions invading major pulmonary vessels
  • Use of oral anticoagulants or platelet inhibitors not allowed except specified exceptions
  • Gastrointestinal disorders with high risk of perforation or fistula within 6 months prior to randomization
  • Major surgery within 8 weeks prior to randomization without complete healing
  • Lesion growth greater than specified thresholds within 2-3 months prior to randomization
  • Documented anaplastic histology at or after recurrence
  • Prior treatment with cabozantinib or BRAF targeted therapy for thyroid cancer
  • Pregnant or breastfeeding women
  • Inability to provide informed consent or no legally authorized representative available
  • QTcF interval greater than 500 ms on ECG after repeat testing
  • Non-English or non-Spanish speakers for quality of life component

AI-Screening

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Trial Site Locations

Total: 112 locations

1

Mercy Hospital Fort Smith

Fort Smith, Arkansas, United States, 72903

Actively Recruiting

2

CARTI Cancer Center

Little Rock, Arkansas, United States, 72205

Actively Recruiting

3

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, United States, 06418

Actively Recruiting

4

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, United States, 06824

Actively Recruiting

5

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, United States, 06033

Actively Recruiting

6

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States, 06830

Actively Recruiting

7

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States, 06437

Actively Recruiting

8

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States, 06105

Actively Recruiting

9

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States, 06510

Actively Recruiting

10

Yale University

New Haven, Connecticut, United States, 06520

Actively Recruiting

11

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, United States, 06473

Actively Recruiting

12

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, United States, 06902

Actively Recruiting

13

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, United States, 06790

Actively Recruiting

14

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States, 06611

Actively Recruiting

15

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States, 06708

Actively Recruiting

16

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States, 06385

Actively Recruiting

17

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States, 83706

Actively Recruiting

18

Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho, United States, 83605

Actively Recruiting

19

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States, 83814

Actively Recruiting

20

Walter Knox Memorial Hospital

Emmett, Idaho, United States, 83617

Suspended

21

Idaho Urologic Institute-Meridian

Meridian, Idaho, United States, 83642

Actively Recruiting

22

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, United States, 83687

Actively Recruiting

23

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States, 83854

Actively Recruiting

24

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, United States, 83864

Actively Recruiting

25

OSF Saint Anthony's Health Center

Alton, Illinois, United States, 62002

Actively Recruiting

26

Saint Mary's Hospital

Centralia, Illinois, United States, 62801

Actively Recruiting

27

Northwestern University

Chicago, Illinois, United States, 60611

Actively Recruiting

28

University of Illinois

Chicago, Illinois, United States, 60612

Actively Recruiting

29

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States, 60115

Actively Recruiting

30

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States, 60134

Actively Recruiting

31

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois, United States, 60026

Actively Recruiting

32

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois, United States, 60030

Actively Recruiting

33

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States, 60045

Actively Recruiting

34

Good Samaritan Regional Health Center

Mount Vernon, Illinois, United States, 62864

Actively Recruiting

35

Northwestern Medicine Orland Park

Orland Park, Illinois, United States, 60462

Actively Recruiting

36

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States, 60555

Actively Recruiting

37

Mercy Hospital

Cedar Rapids, Iowa, United States, 52403

Actively Recruiting

38

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, United States, 52403

Actively Recruiting

39

Central Care Cancer Center - Garden City

Garden City, Kansas, United States, 67846

Actively Recruiting

40

Central Care Cancer Center - Great Bend

Great Bend, Kansas, United States, 67530

Actively Recruiting

41

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, United States, 56601

Actively Recruiting

42

Minnesota Oncology - Burnsville

Burnsville, Minnesota, United States, 55337

Actively Recruiting

43

Cambridge Medical Center

Cambridge, Minnesota, United States, 55008

Actively Recruiting

44

Mercy Hospital

Coon Rapids, Minnesota, United States, 55433

Actively Recruiting

45

Fairview Southdale Hospital

Edina, Minnesota, United States, 55435

Actively Recruiting

46

Fairview Clinics and Surgery Center Maple Grove

Maple Grove, Minnesota, United States, 55369

Actively Recruiting

47

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, United States, 55109

Actively Recruiting

48

Saint John's Hospital - Healtheast

Maplewood, Minnesota, United States, 55109

Actively Recruiting

49

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States, 55407

Actively Recruiting

50

Hennepin County Medical Center

Minneapolis, Minnesota, United States, 55415

Actively Recruiting

51

Health Partners Inc

Minneapolis, Minnesota, United States, 55454

Actively Recruiting

52

Monticello Cancer Center

Monticello, Minnesota, United States, 55362

Actively Recruiting

53

New Ulm Medical Center

New Ulm, Minnesota, United States, 56073

Actively Recruiting

54

Fairview Northland Medical Center

Princeton, Minnesota, United States, 55371

Actively Recruiting

55

North Memorial Medical Health Center

Robbinsdale, Minnesota, United States, 55422

Actively Recruiting

56

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States, 55416

Actively Recruiting

57

Regions Hospital

Saint Paul, Minnesota, United States, 55101

Actively Recruiting

58

United Hospital

Saint Paul, Minnesota, United States, 55102

Actively Recruiting

59

Saint Francis Regional Medical Center

Shakopee, Minnesota, United States, 55379

Actively Recruiting

60

Lakeview Hospital

Stillwater, Minnesota, United States, 55082

Actively Recruiting

61

Sanford Thief River Falls Medical Center

Thief River Falls, Minnesota, United States, 56701

Actively Recruiting

62

Ridgeview Medical Center

Waconia, Minnesota, United States, 55387

Actively Recruiting

63

Rice Memorial Hospital

Willmar, Minnesota, United States, 56201

Actively Recruiting

64

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota, United States, 55125

Actively Recruiting

65

Sanford Cancer Center Worthington

Worthington, Minnesota, United States, 56187

Actively Recruiting

66

Fairview Lakes Medical Center

Wyoming, Minnesota, United States, 55092

Actively Recruiting

67

Saint Louis Cancer and Breast Institute-Ballwin

Ballwin, Missouri, United States, 63011

Actively Recruiting

68

Central Care Cancer Center - Bolivar

Bolivar, Missouri, United States, 65613

Actively Recruiting

69

Cox Cancer Center Branson

Branson, Missouri, United States, 65616

Actively Recruiting

70

Southeast Cancer Center

Cape Girardeau, Missouri, United States, 63703

Actively Recruiting

71

Freeman Health System

Joplin, Missouri, United States, 64804

Actively Recruiting

72

Mercy Hospital Joplin

Joplin, Missouri, United States, 64804

Actively Recruiting

73

Lake Regional Hospital

Osage Beach, Missouri, United States, 65065

Actively Recruiting

74

Delbert Day Cancer Institute at PCRMC

Rolla, Missouri, United States, 65401

Actively Recruiting

75

Mercy Clinic-Rolla-Cancer and Hematology

Rolla, Missouri, United States, 65401

Actively Recruiting

76

Heartland Regional Medical Center

Saint Joseph, Missouri, United States, 64506

Actively Recruiting

77

Mercy Hospital Springfield

Springfield, Missouri, United States, 65804

Actively Recruiting

78

CoxHealth South Hospital

Springfield, Missouri, United States, 65807

Actively Recruiting

79

Saint Louis Cancer and Breast Institute-South City

St Louis, Missouri, United States, 63109

Actively Recruiting

80

Mercy Hospital South

St Louis, Missouri, United States, 63128

Actively Recruiting

81

Mercy Hospital Saint Louis

St Louis, Missouri, United States, 63141

Actively Recruiting

82

Mercy Hospital Washington

Washington, Missouri, United States, 63090

Actively Recruiting

83

Community Hospital of Anaconda

Anaconda, Montana, United States, 59711

Actively Recruiting

84

Billings Clinic Cancer Center

Billings, Montana, United States, 59101

Actively Recruiting

85

Bozeman Health Deaconess Hospital

Bozeman, Montana, United States, 59715

Actively Recruiting

86

Benefis Sletten Cancer Institute

Great Falls, Montana, United States, 59405

Actively Recruiting

87

Great Falls Clinic

Great Falls, Montana, United States, 59405

Actively Recruiting

88

Logan Health Medical Center

Kalispell, Montana, United States, 59901

Actively Recruiting

89

Community Medical Center

Missoula, Montana, United States, 59804

Actively Recruiting

90

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States, 58501

Actively Recruiting

91

Sanford South University Medical Center

Fargo, North Dakota, United States, 58103

Actively Recruiting

92

Southpointe-Sanford Medical Center Fargo

Fargo, North Dakota, United States, 58103

Actively Recruiting

93

Sanford Medical Center Fargo

Fargo, North Dakota, United States, 58104

Actively Recruiting

94

Sanford Broadway Medical Center

Fargo, North Dakota, United States, 58122

Actively Recruiting

95

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States, 58122

Actively Recruiting

96

Mercy Hospital Oklahoma City

Oklahoma City, Oklahoma, United States, 73120

Actively Recruiting

97

Saint Alphonsus Cancer Care Center-Baker City

Baker City, Oregon, United States, 97814

Actively Recruiting

98

Saint Alphonsus Cancer Care Center-Ontario

Ontario, Oregon, United States, 97914

Actively Recruiting

99

UPMC Hillman Cancer Center Erie

Erie, Pennsylvania, United States, 16505

Actively Recruiting

100

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States, 15232

Actively Recruiting

101

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, United States, 02891

Actively Recruiting

102

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States, 57104

Actively Recruiting

103

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States, 57117-5134

Actively Recruiting

104

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, United States, 54701

Actively Recruiting

105

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States, 54449

Actively Recruiting

106

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, United States, 54548

Actively Recruiting

107

Cancer Center of Western Wisconsin

New Richmond, Wisconsin, United States, 54017

Actively Recruiting

108

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, United States, 54868

Actively Recruiting

109

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, United States, 54482

Actively Recruiting

110

Marshfield Medical Center - Weston

Weston, Wisconsin, United States, 54476

Actively Recruiting

111

Billings Clinic-Cody

Cody, Wyoming, United States, 82414

Actively Recruiting

112

Welch Cancer Center

Sheridan, Wyoming, United States, 82801

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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