Actively Recruiting
A Phase I Trial of Concurrent Intensity Modulated Radiation Therapy (IMRT) and Dabrafenib/Trametinib in BRAF Mutated Anaplastic Thyroid Cancer
Led by City of Hope Medical Center · Updated on 2026-04-08
6
Participants Needed
3
Research Sites
N/A
Total Duration
On this page
Sponsors
C
City of Hope Medical Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating how well a combination of dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) works in treating patients with BRAF mutated anaplastic thyroid cancer. This study aims to assess the safety, tolerability, and effectiveness of combining these treatments to potentially kill more tumor cells. It is a phase 1 trial focusing on patients with aggressive thyroid cancer that has specific BRAF mutations. Patients first receive oral dabrafenib twice daily and trametinib once daily for 7 to 28 days if their disease does not progress and they tolerate the drugs. Those with tumors that can be surgically removed may have surgery followed by radiation therapy combined with dabrafenib and trametinib. Radiation is delivered Monday through Friday over 6.5 weeks during concurrent drug treatment. After radiation, patients continue the oral drugs for four weeks and then may have ongoing maintenance treatment depending on residual disease status. Throughout the study, participants undergo various assessments including monitoring for side effects, tumor response, and survival outcomes. Researchers track blood levels of the drugs and study mechanisms of resistance. After study treatment ends, patients are followed every two months for one year to monitor their health. The main goal is to identify the highest safe dose of the combined therapy while evaluating its effects on disease progression and survival.
CONDITIONS
Brief Title
Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of anaplastic thyroid cancer confirmed by pathology
- Presence of BRAF V600E or V600K mutation in tumor tissue
- Eastern Cooperative Oncology Group (ECOG) performance status less than 2
- Absolute neutrophil count greater than 1,000/mcL
- Hemoglobin level of 9.0 g/dl or higher (transfusion allowed to reach this)
- Platelet count greater than 75,000/mcL
- Total bilirubin less than 1.5 times the institutional upper limit of normal unless due to Gilbert's disease
- AST and ALT less than 2.5 times the institutional upper limit of normal
- Serum creatinine less than 1.5 times the institutional upper limit of normal
- Negative pregnancy test within 14 days before starting study medication for females of childbearing potential
- Use of effective contraception during study and for specified periods after treatment for both females and males
- Ability to understand and sign informed consent
You will not qualify if you...
- Candidates for surgery with resectable stage IVA anaplastic thyroid cancer who wish to proceed with surgery
- Prior external beam radiotherapy to neck or chest overlapping planned treatment fields
- Cytotoxic chemotherapy, stereotactic brain radiation, or external beam radiation within 2 weeks before study start
- Oral multikinase inhibitors within 1 week before study start
- Unresolved side effects from previous cancer therapy above grade 2 except alopecia
- Previous treatment with potent BRAF or MEK inhibitors (except sorafenib)
- Receiving other investigational agents
- Taking any prohibited medications
- History of other active malignancy needing treatment
- Uncontrolled brain metastases or use of certain anti-epileptic drugs
- History of retinal vein occlusion, central serous retinopathy, uncontrolled glaucoma, or ocular hypertension
- Heart failure class II, III, or IV
- Corrected QT interval ≥480 msecs (≥500 msec with bundle branch block)
- Uncontrolled illnesses such as active infection, heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social issues limiting compliance
- Pregnant or nursing women
- Known HIV positive or on combination antiretroviral therapy
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 7 to 28 days
Participants receive dabrafenib and trametinib orally for 7 to 28 days without disease progression or unacceptable toxicity.
Visits as needed during induction period
Duration - Approximately 17 days (3 days after treatment plus 14 days recovery)
Participants with resectable disease may undergo surgery 3 days after stopping dabrafenib and trametinib, followed by recovery before radiation therapy.
1 to 2 visits depending on surgical scheduling and wound healing
Duration - 6.5 weeks
Participants receive dabrafenib and trametinib orally while undergoing intensity modulated radiation therapy (IMRT) Monday through Friday over 6.5 weeks without disease progression or unacceptable toxicity.
Daily visits Monday through Friday for radiation over 6.5 weeks
Duration - 4 weeks
Participants continue dabrafenib and trametinib orally for 4 weeks after radiation therapy in the absence of disease progression and unacceptable toxicity.
Visits as needed during post-radiation period
Duration - Variable until complete response or disease progression
Participants with residual disease continue dabrafenib and trametinib orally until complete response or disease progression, then stop treatment after 8 weeks or restart if recurrence occurs. Participants with no residual disease stop treatment after radiation.
Visits as needed during maintenance therapy
Duration - 1 year
After completing study treatment, participants are followed up every 2 months for 1 year to monitor health and disease status.
Visits every 2 months for 1 year
Trial Site Locations
Total: 3 locations
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
2
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Actively Recruiting
3
Univ of Texas-M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
S
Sasan Fazeli, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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