RECRUITING

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

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Randomized Phase III Study of BRAF-Targeted Therapy vs Cabozantinib in RAI-Refractory Differentiated Thyroid Cancer With BRAF V600Em

Quick Facts

Study Start:2024-08-22
Study Completion:2030-09-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06475989

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Patient must be ≥ 18 years of age
  2. * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  3. * 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):
  4. * 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.
  5. * Follicular thyroid carcinoma including histological variants of follicular thyroid carcinoma (FTC) such as Hürthle cell, clear cell, insular, and poorly differentiated
  6. * Patient must have been previously treated with or deemed ineligible for treatment with Iodine-131 for DTC, and must be receiving thyroxine suppression therapy
  7. * 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.
  8. * NOTE: Up to two prior VEGFR-targeting TKI agents are allowed including, but not limited to lenvatinib and sorafenib
  9. * 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
  10. * 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
  11. * Patient must not have any of the following cardiovascular and thromboembolic disorders or medical conditions:
  12. * Congestive heart failure class 3 or 4 as defined by the New York Heart Association, unstable angina pectoris, or serious cardiac arrhythmias.
  13. * Uncontrolled hypertension defined as sustained blood pressure \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment.
  14. * 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
  15. * 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
  16. * Patient must not have any cavitating pulmonary lesion(s) or lesions invading major pulmonary blood vessels
  17. * Patient must not be on any concomitant anticoagulation with oral anticoagulants or platelet inhibitors, except for the following allowed agents:
  18. * Low-dose aspirin for cardioprotection.
  19. * 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
  20. * Patient must not have any gastrointestinal (GI) disorders associated with a high risk of perforation or fistula formation:
  21. * 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
  22. * Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months prior to randomization
  23. * 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
  24. * 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
  25. * 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
  26. * Patient must not have had prior treatment with cabozantinib or any prior BRAF targeted therapy for thyroid cancer
  27. * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
  28. * Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 2 weeks after the last dose of dabrafenib and 4 months after the last dose of trametinib or cabozantinib. Patients must also not breastfeed while on study treatment and for 2 weeks after the last dose of dabrafenib and for 4 months after the last dose of trametinib or cabozantinib.
  29. * NOTE: Patients of childbearing potential who are on hormonal contraceptives may be at risks because dabrafenib may decrease the efficacy of hormonal contraceptives. An effective non-hormonal contraception should be used during therapy and for 2 weeks following discontinuation of dabrafenib and at least 4 months following the last dose of trametinib and cabozantinib
  30. * Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  31. * Hemoglobulin (Hgb) ≥ 8 g/dL obtained ≤ 28 days prior to protocol randomization
  32. * Leukocytes ≥ 3,000/mcL obtained ≤ 28 days prior to protocol randomization
  33. * Absolute neutrophil count (ANC) ≥ 1,500/mcL obtained ≤ 28 days prior to protocol randomization
  34. * Platelets ≥ 100,000/mcL obtained ≤ 28 days prior to protocol randomization
  35. * Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) obtained ≤ 28 days prior to protocol randomization
  36. * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 × institutional ULN or \< 5.0 x ULN with the presence of hepatic metastasis obtained ≤ 28 days prior to protocol randomization
  37. * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² obtained ≤ 28 days prior to protocol randomization
  38. * Urine protein/creatinine (UPC) ratio ≥ 1 obtained ≤ 28 days prior to protocol randomization
  39. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
  40. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  41. * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  42. * Patients with treated brain metastases are eligible if follow-up brain imaging obtained after central nervous system (CNS)-directed therapy (radiotherapy and/or surgery) shows no evidence of progression. CNS disease must be stable for at least 4 weeks prior to randomization; patients must be neurologically asymptomatic and without corticosteroid treatment at time of randomization
  43. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  44. * Patients must have corrected QT interval calculated by the Fridericia formula (QTcF) ≤ 500 ms obtained within 28 days prior to randomization.
  45. * NOTE: If a single electrocardiogram (ECG) shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 minutes (min) must be performed within 30 min after the initial ECG, and the average of these 3 consecutive results for QTcF will be used to determine eligibility
  46. * Patient must be English or Spanish speaking to be eligible for the quality of life (QOL) component of the study.
  47. * NOTE: Sites cannot translate the associated QOL forms
  1. Pregnancy or breastfeeding
  2. Severe psychiatric disorders
  3. Active substance abuse
  4. Unstable medical conditions
  5. Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Lova Sun
PRINCIPAL_INVESTIGATOR
ECOG-ACRIN Cancer Research Group

Study Locations (Sites)

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
Saint Louis Cancer and Breast Institute-South City
Saint Louis, Missouri, 63109
United States
Mercy Hospital South
Saint Louis, Missouri, 63128
United States
Mercy Hospital Saint Louis
Saint Louis, Missouri, 63141
United States
Mercy Hospital Springfield
Springfield, Missouri, 65804
United States
CoxHealth South Hospital
Springfield, Missouri, 65807
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

Collaborators and Investigators

Sponsor: ECOG-ACRIN Cancer Research Group

  • Lova Sun, PRINCIPAL_INVESTIGATOR, ECOG-ACRIN Cancer Research Group

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-22
Study Completion Date2030-09-30

Study Record Updates

Study Start Date2024-08-22
Study Completion Date2030-09-30

Terms related to this study

Additional Relevant MeSH Terms

  • Refractory Differentiated Thyroid Gland Carcinoma