Pulsed Stereotactic Ablative Radiotherapy (PULSAR) With Systematic Therapy for Thyroid Cancer
1 other identifier
interventional
12
1 country
1
Brief Summary
This study is a single institution non-randomized phase 2 trial looking at the effect of Pulsed Stereotactic Ablative Radiotherapy (PULSAR) followed by neoadjuvant chemotherapy dabrafenib and trametinib (DT) with or without pembrolizumab on patients with advanced anaplastic thyroid carcinoma (ATC). Pembrolizumab will be administered per standard of care (SOC) only to patients who are PDL1 positive at screening.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Dec 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 14, 2026
CompletedFirst Posted
Study publicly available on registry
October 21, 2026
CompletedStudy Start
First participant enrolled
December 31, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
April 8, 2029
Study Completion
Last participant's last visit for all outcomes
May 13, 2029
October 21, 2026
October 1, 2026
2.3 years
October 14, 2026
October 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Rate of 30-day mortality
Defined as death considered possibly, probably, or definitely related to PULSAR-DT +/- pembrolizumab occurring within 30 days after any administered PULSAR fraction. The treatment-related mortality rate will be calculated as the number of participants experiencing a qualifying death divided by the total number of participants in the Safety Analysis Set (all enrolled participants who receive at least one fraction or dose of any treatment, including PULSAR, dabrafenib, trametinib, or pembrolizumab) and will be presented with an exact binomial 95% confidence interval (CI).
Within 30 days after any administered PULSAR fraction (up to approximately 9 weeks)
Objective response rate (ORR) at 1st restaging
ORR is defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) as assessed by RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
At 1st restaging (estimated to be 4 weeks)
Objective response rate (ORR) at 2nd restaging
ORR is defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) as assessed by RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
At 2nd restaging (estimated to be 13-14 weeks)
Secondary Outcomes (4)
Feasibility as measured by the total percentage of participants who are able to undergo surgical resection following completion of neoadjuvant PULSAR-DT +/- pembrolizumab
Baseline until completion of surgery (total estimated time 5-19 weeks)
Pill compliance - dabrafenib
Start of dabrafenib treatment to completion of treatment (total estimated time 9 weeks)
Pill compliance - trametinib
Start of trametinib treatment to completion of treatment (total estimated time 9 weeks)
Number of planned PULSAR pulses completed by participants
At completion of PULSAR (estimated to be 5 weeks)
Study Arms (1)
PULSAR + DT +/- Pembrolizumab
EXPERIMENTALAll patients will receive 2 pulses of PULSAR spaced 2 weeks apart, followed by restaging scans. Those determined to be resectable will undergo surgery followed by maintenance dabrafenib + trametinib (DT) +/- pembrolizumab (if applicable). Those who have a partial response or stable disease will then undergo a 3rd pulse of PULSAR, followed by two cycles of DT +/- pembrolizumab. Patients will again undergo restaging scans and if they are determined to be resectable, they may undergo one bridging cycle of DT +/- pembrolizumab if possible prior to surgery. After undergoing surgery, patients will undergo maintenance DT +/- pembrolizumab. If they are still unresectable, they will start on palliative DT +/- pembrolizumab. If patients experience disease progression at any of the restaging scans, patients may receive salvage DT +/- pembrolizumab on study or discontinue treatment.
Interventions
Dabrafenib is administered as a 150 mg pill that is taken twice daily, 12 hours a part. Dabrafenib is taken as part of a 3 week cycle.
Ethos is a unique ring-gantry CT-guided linear accelerator notable for having a dedicated artificial intelligence treatment planning system to allow for online adaptive radiotherapy.
Trametinib is administered as a 2mg pill taken once daily. Trametinib is taken as a part of a 3-week cycle.
Pembrolizumab is administered intravenously per standard of care on the Day 1 of a 3 week cycle.
PULSAR is a radiation treatment (10Gy x 1 fraction) administered up to 3 times in the neoadjuvant setting.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed anaplastic thyroid cancer, AJCC 8th Edition Stage IVB-C.
- Disease must be deemed unresectable, or resectable only with unacceptable functional morbidity (e.g., requiring total laryngectomy, total pharyngectomy, or extensive aerodigestive resection), as determined by multidisciplinary tumor board consensus.
- BRAF-V600E positive by IHC.
- Measurable disease per RECIST 1.1.
- At least 18 years of age.
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
- Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance \> 30 mL/min by Cockcroft-Gault
- Ability to swallow pills or have percutaneous enteric access (G-tube or J-tube) allowing for administration of dabrafenib-trametinib pills.
- Dabrafenib and trametinib are known teratogenic agents, and dabrafenib can render hormonal contraceptives ineffective. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 2 weeks after the last dose of dabrafenib or 4 months after the last dose of trametinib, whichever dose is later. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform the treating physician immediately.
- +1 more criteria
You may not qualify if:
- Prior radiation therapy to the head and neck or spinal cord.
- Prior systemic therapy for thyroid cancer.
- Prior immunotherapy for any indication.
- Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib, trametinib, pembrolizumab, or other agents used in the study.
- Use of any strong inhibitors of CYP3A4 or CYP2C8, or sensitive substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2B6, within 7 days prior to enrollment and during the course of this study.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. - with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Prior allogeneic tissue/solid organ transplant.
- Use of any immunosuppressive medications within 7 days prior to enrollment.
- Use of live or live attenuated vaccines within 30 days prior to enrollment.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 5 days prior to enrollment.
- HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
- Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nikhil Rammohan, MD, PhD
Washington University School of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 14, 2026
First Posted
October 21, 2026
Study Start (Estimated)
December 31, 2026
Primary Completion (Estimated)
April 8, 2029
Study Completion (Estimated)
May 13, 2029
Last Updated
October 21, 2026
Record last verified: 2026-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Data will be available beginning after publication of the primary study results and will remain available for a defined period thereafter (e.g., up to 36 months after publication, or per institutional policy). Requests outside this window may still be considered at the discretion of the PI and sponsoring institution.
- Access Criteria
- Researchers must submit a formal written request to the PI describing the requesting investigator \& institution, the specific data elements requested, a detailed research question, analysis plan, \& the intended use of the data. Each request will be individually reviewed by the PI (in consultation with the study team \&, where applicable, the sponsoring institution and IRB). Access will be granted only after: (1) the PI's written approval of the specific request; (2) confirmation that the proposed use is consistent with participant consent \& ethical approvals; \& (3) execution of a data-use agreement. The PI reserves the right to decline requests that are scientifically unsound, that conflict with ongoing or planned analyses, that risk participant re-identification, or that fall outside the scope of the original consent. Approved data will be transferred through a secure, access-controlled method specified in the executed DUA.
De-identified individual participant data (IPD) that underlie the results reported in any publication or presentation arising from this study may be made available to qualified external researchers. All requests for data sharing are subject to prior review \& written approval by the study Principal Investigator (PI) before any data are released. No individual participant data will be shared without advance consultation with, \& documented authorization from, the PI. Data will be shared only for scientifically sound proposals that are consistent with the consent provided by study participants, that do not overlap with analyses planned or ongoing by the study team, \& that comply with all applicable institutional, IRB, privacy (e.g., HIPAA), \& data-use requirements. All released datasets will be de-identified in accordance with applicable regulations, \& a data-use agreement (DUA) executed between the requesting institution \& the sponsoring institution will be required prior to transfer.