BRAF NP_004324.2:p.V600EPhase 1NCT03975231
Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer
A Phase 1 study testing Dabrafenib, Intensity-Modulated Radiation Therapy and Trametinib in people with BRAF NP_004324.2:p.V600E and BRAF V600K Mutation Present, run by City of Hope Medical Center at 3 sites in United States.
Trial summary
This trial studies how well dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) work together in treating patients with BRAF mutated anaplastic thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- BRAF NP_004324.2:p.V600E, BRAF V600K Mutation Present, Thyroid Gland Anaplastic Carcinoma
- What is being tested?
- Dabrafenib, Intensity-Modulated Radiation Therapy and Trametinib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Sep 2020to 5 Oct 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologic (histologic or cytologic) diagnosis of anaplastic thyroid cancer (a diagnosis that is noted to be ?consistent with anaplastic thyroid cancer? with the presence of a thyroid mass is acceptable; pathology showing additional types of thyroid cancer is allowed)
- Note: Tissue collection for central review is mandatory, but central review is not required for eligibility. Due to the aggressiveness of this disease, treatment will be started prior to central review.
- Presence of BRAF mutation (V600E or V600K) in tumor tissue.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2.
- Absolute neutrophil count > 1,000/mcL.
- Hemoglobin >= 9.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable).
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- Platelets > 75,000/mcL.
- Total bilirubin < 1.5 x institutional upper limit of normal (unless due to Gilbert?s disease).
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal.
- Serum creatinine < 1.5 x institutional upper limit of normal.
- Female patients of childbearing potential are required to have a negative serum pregnancy test within 14 days prior to the first dose of study medication.
- Females are required to use an effective method of contraception from the time of negative serum pregnancy test, throughout the study duration, and for 4 months after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study enrollment, for the duration of study participation, and for 16 weeks after completion of the last dose of study drug.
- Specific contraception requirements for females: Female subjects of childbearing potential must not become pregnant and are required to be sexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%. Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception. Contraceptive methods with a failure rate of < 1% include the following:
- Intrauterine device (IUD) or intrauterine system (IUS) that meets the < 1% failure rate as stated in the product label,
- Male partner sterilization (vasectomy with documentation of Azoospermia) prior to the female subject's entry into the study, and this male is patient?s sole sexual partner. For this definition, ?documented? refers to the outcome of the investigator's/qualified physician designee?s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject?s medical records.
- Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam, gel, film, cream, suppository) These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring subjects understand how to properly use these methods of contraception.
- Specific contraception requirements for males: To prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject?s semen, male subjects must use one of the following contraceptive methods during the study and for a total of 16 weeks following the last dose of study drug (based upon the lifecycle of sperm):
- Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject for 14 days prior to first dose of study drug, through the dosing period, and for at least 16 weeks after the last dose of study drug. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Condom (during non-vaginal intercourse with any partner - male or female) OR
- Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female).
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients with resectable stage IVA anaplastic thyroid cancer who are candidates for surgery and wish to proceed with surgery.
- Patients who have had external beam radiotherapy to neck or chest for cancer that would result in overlap of radiation therapy fields.
- Patients who have had cytotoxic chemotherapy, stereotactic brain radiation or external beam radiation within 2 weeks prior to study treatment initiation.
- Patients who have had oral multikinase inhibitors within 1 week prior to study treatment initiation.
- Patients that have not recovered from adverse events related to prior therapy for cancer to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 grade 2 or less except for alopecia.
- Patients previously treated with potent BRAF inhibitor or MEK inhibitor. Previous treatment with sorafenib is permitted.
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- Patients that are receiving any other investigational agent.
- Patients that are currently taking any prohibitive medication.
- Patients with a history of other active malignancy requiring cancer treatment.
- Patients with uncontrolled brain metastases. Patients who are on a stable dose of corticosteroids for more than 1 week or off corticosteroids for 2 weeks prior to study enrollment can be enrolled. Enzyme-inducing anti-epileptic drugs are not permitted.
- Patients with a known history of retinal vein occlusion (RVO), central serous retinopathy (CSR), uncontrolled glaucoma or ocular hypertension.
- Patients with class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Corrected QT (QTc) interval greater than or equal to 480 msecs (>= 500 msec for subjects with Bundle Branch Block).
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women and nursing women are excluded from this study because dabrafenib has the potential for teratogenic or abortifacient effects. In embroyfetal developmental studies in rats, developmental toxicities including reduced fetal body weight, embryo-lethality, cardiac ventricular septal defect malformations, delayed skeletal development and variation in thymic shape have been observed.
- Known human immunodeficiency virus (HIV)-positive patients or those on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drugs.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
City of Hope Medical Center
Duarte, California, 91010
Univ of Texas-M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase I Trial of Concurrent Intensity Modulated Radiation Therapy (IMRT) and Dabrafenib/Trametinib in BRAF Mutated Anaplastic Thyroid Cancer
This trial studies how well dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) work together in treating patients with BRAF mutated anaplastic thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving dabrafenib, trametinib, and IMRT together may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability (maximum tolerated dose [MTD]) of concurrent intensity modulated radiation therapy (IMRT) and BRAF-MEK inhibitors dabrafenib and trametinib in patients with BRAF-mutated anaplastic thyroid cancer.
SECONDARY OBJECTIVES:
- To assess overall objective response rate, time to progression of local recurrence, progression free survival and overall survival.
II. To assess pharmacokinetics during concurrent IMRT and dabrafenib plus trametinib therapy.
III. To assess pharmacodynamics of dabrafenib plus trametinib induction therapy.
IV. To assess mechanism of resistance to dabrafenib plus trametinib and radiation therapy.
OUTLINE: This is a dose-escalation study of dabrafenib.
INDUCTION: Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 7-28 days in the absence of disease progression and unacceptable toxicity.
OPTIONAL SURGERY: Patients with resectable disease may undergo surgery 3 days after stop treatment of dabrafenib/trametinib, and move to Concurrent Radiation 14 days after surgery provided that surgical wound has healed. All other patients continue to receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity.
CONCURRENT RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD at weeks 6-7. Within 2.5 hours of morning doses of dabrafenib/trametinib administration, patients undergo intensity modulated radiation therapy (IMRT) on Monday-Friday delivered over 6.5 weeks in the absence of disease progression or unacceptable toxicity.
POST-RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD for 4 weeks in the absence of disease progression and unacceptable toxicity.
MAINTENANCE: Patients with residual disease receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity. Patients stop dabrafenib and trametinib 8 weeks after achieving complete response. Patients with no residual disease stop dabrafenib and trametinib, with the option of restarting dabrafenib and trametinib at time of disease recurrence.
After completion of study treatment, patients are followed up every 2 months for 1 year.
- Being tested
- Dabrafenib, Intensity-Modulated Radiation Therapy, Trametinib
- Medical subject headings
- Thyroid Carcinoma, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabrafenibDrug
Also called BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436
Given PO
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy
Undergo IMRT
TrametinibDrug
Also called GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dabrafenib, trametinib, IMRT) | Experimental | See Detailed Description Receives: Drug: Dabrafenib; Radiation: Intensity-Modulated Radiation Therapy; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT)
Measured: 1 year
Secondary outcomes (4)
Objective response rate
Will be defined as the proportion of patients who have a partial response (PR), or complete response (CR) within the first 4 weeks of IMRT. Complete response (CR) and partial response (PR) will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be calculated with the exact binomial 95% confidence intervals.
Measured: 1 year
Time to progression for local disease recurrence
Will be evaluated by RECIST criteria for disease limited to the radiation field (neck) following the first set of scans after completion of IMRT. Estimated by Kaplan-Meier method.
Measured: 1 year
Overall survival
Estimated by Kaplan-Meier method.
Measured: From the start date of the treatment to the date of death, assessed up to 1 year
Progression free survival
Estimated by Kaplan-Meier method.
Measured: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2019
- Study start14 Sep 2020
- Primary completion5 Oct 2027 (estimated)
- Study completion5 Oct 2027 (estimated)
Why it stopped: Accrual goal met
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BRAF NP_004324.2:p.V600EStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sasan Fazeli, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03975231
- Sponsor's protocol ID
- 21308
- Other IDs
- NCI-2019-02745, R01CA246553, OSU-17277
- Status last verified
- Oct 2026
- First submitted
- 3 Jun 2019
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Concurrent Intensity Modulated Radiation Therapy (IMRT) and Dabrafenib/Trametinib in BRAF Mutated Anaplastic Thyroid Cancer
- ClinicalTrials.gov ID
- NCT03975231
- Acronym / sponsor ID
- 21308
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Accrual goal met
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 5 Oct 2027 (estimated)
- Study completion
- 5 Oct 2027 (estimated)
- First posted
- 5 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial studies how well dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) work together in treating patients with BRAF mutated anaplastic thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving dabrafenib, trametinib, and IMRT together may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability (maximum tolerated dose [MTD]) of concurrent intensity modulated radiation therapy (IMRT) and BRAF-MEK inhibitors dabrafenib and trametinib in patients with BRAF-mutated anaplastic thyroid cancer.
SECONDARY OBJECTIVES:
- To assess overall objective response rate, time to progression of local recurrence, progression free survival and overall survival.
II. To assess pharmacokinetics during concurrent IMRT and dabrafenib plus trametinib therapy.
III. To assess pharmacodynamics of dabrafenib plus trametinib induction therapy.
IV. To assess mechanism of resistance to dabrafenib plus trametinib and radiation therapy.
OUTLINE: This is a dose-escalation study of dabrafenib.
INDUCTION: Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 7-28 days in the absence of disease progression and unacceptable toxicity.
OPTIONAL SURGERY: Patients with resectable disease may undergo surgery 3 days after stop treatment of dabrafenib/trametinib, and move to Concurrent Radiation 14 days after surgery provided that surgical wound has healed. All other patients continue to receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity.
CONCURRENT RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD at weeks 6-7. Within 2.5 hours of morning doses of dabrafenib/trametinib administration, patients undergo intensity modulated radiation therapy (IMRT) on Monday-Friday delivered over 6.5 weeks in the absence of disease progression or unacceptable toxicity.
POST-RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD for 4 weeks in the absence of disease progression and unacceptable toxicity.
MAINTENANCE: Patients with residual disease receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity. Patients stop dabrafenib and trametinib 8 weeks after achieving complete response. Patients with no residual disease stop dabrafenib and trametinib, with the option of restarting dabrafenib and trametinib at time of disease recurrence.
After completion of study treatment, patients are followed up every 2 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dabrafenib, trametinib, IMRT) | Experimental | Drug: Dabrafenib, Radiation: Intensity-Modulated Radiation Therapy, Drug: TrametinibSee Detailed Description |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Pathologic (histologic or cytologic) diagnosis of anaplastic thyroid cancer (a diagnosis that is noted to be ?consistent with anaplastic thyroid cancer? with the presence of a thyroid mass is acceptable; pathology showing additional types of thyroid cancer is allowed)
- Presence of BRAF mutation (V600E or V600K) in tumor tissue.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2.
- Absolute neutrophil count > 1,000/mcL.
- Hemoglobin >= 9.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable).
Key exclusion criteria (16 listed)
- Patients with resectable stage IVA anaplastic thyroid cancer who are candidates for surgery and wish to proceed with surgery.
- Patients who have had external beam radiotherapy to neck or chest for cancer that would result in overlap of radiation therapy fields.
- Patients who have had cytotoxic chemotherapy, stereotactic brain radiation or external beam radiation within 2 weeks prior to study treatment initiation.
- Patients who have had oral multikinase inhibitors within 1 week prior to study treatment initiation.
- Patients that have not recovered from adverse events related to prior therapy for cancer to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 grade 2 or less except for alopecia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DabrafenibAlso: BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436Given PO | Drug | Treatment (dabrafenib, trametinib, IMRT) |
| Intensity-Modulated Radiation TherapyAlso: IMRT, Intensity Modulated RT, Intensity-Modulated RadiotherapyUndergo IMRT | Radiation | Treatment (dabrafenib, trametinib, IMRT) |
| TrametinibAlso: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, MekinistGiven PO | Drug | Treatment (dabrafenib, trametinib, IMRT) |
Primary outcome
Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT)
Time frame: 1 year
4 secondary outcomes
Objective response rate
Time frame: 1 year
Time to progression for local disease recurrence
Time frame: 1 year
Overall survival
Time frame: From the start date of the treatment to the date of death, assessed up to 1 year
Progression free survival
Time frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sasan Fazeli, MD principal investigator
City of Hope Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dabrafenib, Intensity-Modulated Radiation Therapy and Trametinib in people with BRAF NP_004324.2:p.V600E and BRAF V600K Mutation Present, run by City of Hope Medical Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.