Trial Title:
Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer
NCT ID:
NCT06475989
Condition:
Refractory Differentiated Thyroid Gland Carcinoma
Conditions: Official terms:
Thyroid Neoplasms
Thyroid Diseases
Trametinib
Dabrafenib
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Arm A (Dabrafenib and trametinib)
Arm group label:
Arm B (Cabozantinib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Cabozantinib
Description:
Given PO
Arm group label:
Arm B (Cabozantinib)
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Arm A (Dabrafenib and trametinib)
Arm group label:
Arm B (Cabozantinib)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Dabrafenib
Description:
Given PO
Arm group label:
Arm A (Dabrafenib and trametinib)
Other name:
BRAF Inhibitor GSK2118436
Other name:
GSK-2118436
Other name:
GSK-2118436A
Other name:
GSK2118436
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm A (Dabrafenib and trametinib)
Arm group label:
Arm B (Cabozantinib)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary study
Arm group label:
Arm A (Dabrafenib and trametinib)
Arm group label:
Arm B (Cabozantinib)
Intervention type:
Drug
Intervention name:
Trametinib
Description:
Given PO
Arm group label:
Arm A (Dabrafenib and trametinib)
Other name:
GSK 1120212
Other name:
GSK-1120212
Other name:
GSK1120212
Other name:
JTP-74057
Other name:
MEK Inhibitor GSK1120212
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.
Detailed description:
PRIMARY OBJECTIVE:
I. To compare progression-free survival (PFS) in patients with BRAF V600Em differentiated
thyroid cancer who progressed on frontline multikinase inhibitor treated with
dabrafenib/trametinib or cabozantinib.
SECONDARY OBJECTIVES:
I. To compare the objective response rate in patients with BRAF V600Em differentiated
thyroid cancer that progressed on frontline multikinase inhibitor treated with
dabrafenib/trametinib or cabozantinib.
II. To compare the duration of response in patients with BRAF V600Em differentiated
thyroid cancer that progressed on frontline multikinase inhibitor treated with
dabrafenib/trametinib or cabozantinib.
III. To compare the overall survival in patients with BRAF V600Em differentiated thyroid
cancer that progressed on frontline multikinase inhibitor treated with
dabrafenib/trametinib or cabozantinib.
IV. To compare the PFS2 in patients with BRAF V600Em differentiated thyroid cancer that
progressed on frontline multikinase inhibitor treated with dabrafenib/trametinib or
cabozantinib.
V. To compare the safety/tolerability in patients with BRAF V600Em differentiated thyroid
cancer that progressed on frontline multikinase inhibitor treated with
dabrafenib/trametinib or cabozantinib.
QUALITY OF LIFE OBJECTIVE:
I. To assess patient tolerability of treatment using the Functional Assessment Cancer
Therapy General (FACT G)P5 and general quality of life using the FACT-G7.
OUTLINE: Patients are randomized to 1 of 2 arms. Patients may crossover to other
treatment arm at the time of progression.
ARM A: Patients receive dabrafenib orally (PO) twice per day (BID) and trametinib PO once
per day (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of
disease progression or unacceptable toxicity. Patients undergo computed tomography (CT)
scan, blood sample collection and may undergo magnetic resonance imaging (MRI) throughout
the study.
ARM B: Patients 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.
After completion of study treatment, patients are followed up every 3 months for 2 years
and then every 6 months thereafter up to 5 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Patient must not have had prior treatment with cabozantinib or any prior BRAF
targeted therapy for thyroid cancer
- 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.
All patients of childbearing potential must have a blood test or urine study within 14
days prior to randomization to rule out pregnancy.
A patient of childbearing potential is defined as anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or
bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following
cancer therapy does not rule out childbearing potential) for at least 24 consecutive
months (i.e., has had menses at any time in the preceding 24 consecutive months).
- 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.
- 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
- 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
- Hemoglobulin (Hgb) ≥ 8 g/dL obtained ≤ 28 days prior to protocol randomization
- Leukocytes ≥ 3,000/mcL obtained ≤ 28 days prior to protocol randomization
- Absolute neutrophil count (ANC) ≥ 1,500/mcL obtained ≤ 28 days prior to protocol
randomization
- Platelets ≥ 100,000/mcL obtained ≤ 28 days prior to protocol randomization
- Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) obtained ≤ 28 days
prior to protocol randomization
- 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
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² obtained ≤ 28 days
prior to protocol randomization
- Urine protein/creatinine (UPC) ratio ≥ 1 obtained ≤ 28 days prior to protocol
randomization
- 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
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- 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
- 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
- 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
- Patients must have corrected QT interval calculated by the Fridericia formula (QTcF)
≤ 500 ms obtained within 28 days prior to randomization.
- 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
- Patient must be English or Spanish speaking to be eligible for the quality of life
(QOL) component of the study.
- NOTE: Sites cannot translate the associated QOL forms
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
September 13, 2024
Completion date:
September 30, 2030
Lead sponsor:
Agency:
ECOG-ACRIN Cancer Research Group
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Eastern Cooperative Oncology Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06475989
