Differentiated Thyroid CancerPhase 2NCT04321954
Lenvatinib in Locally Advanced Invasive Thyroid Cancer
A Phase 2 study testing LENVATINIB in people with Differentiated Thyroid Cancer and Advanced Cancer, run by Massachusetts Eye and Ear Infirmary at 3 sites in United States.
Trial summary
This research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC). This research study involves a study drug called lenvatinib Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Differentiated Thyroid Cancer, Advanced Cancer
- What is being tested?
- LENVATINIB
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesUnited States
- Study dates
- 9 Mar 2021to 27 May 2026
- Phase
- Phase 2
- 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
- 18 years of age at the time of informed consent and willing and able to provide written informed consent for the trial.
- Adult participants who are either initially diagnosed with locally advanced thyroid neoplasm or have experienced persistent or recurrent thyroid and/or cervical nodal recurrent DTC (participants with M1 disease are allowed, AJCC 8th edition stage I-IVb)), including:
- a. Papillary thyroid carcinoma (PTC) - classical and variants
- Follicular variant
- Variants including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma
- b. Follicular thyroid carcinoma (FTC)
Show all 34Show fewer
- c. Hürthle cell carcinoma
- d. Poorly differentiated thyroid carcinoma
- e. Cytologically confirmed thyroid neoplasm, Bethesda 3, 4 and 5
- Evidence of extrathyroidal extension and/or locally invasive disease and deemed at risk for R2 resection by treating team on clinical and/or fiberoptic examination and/or radiographic evaluation in the primary or recurrent setting. Evidence of "at risk for R2 resection" includes:
- a. Vocal cord paralysis by fiberoptic examination
- b. Extrathyroid and/or extranodal extension on CT or MRI, including tracheal and/or laryngeal cartilage invasion, esophageal involvement, and/or involvement of perithyroid muscles (e.g. strap, sternocleidomastoid, inferior constrictor muscles) or bone involvement
- c. Extension into the mediastinum with visceral and/or vascular involvement
- d. Involvement of the carotid artery or other major vessel by 180 degrees or more (exclusive of complete encasement)
- e. Other factors that make the participant to be "at risk for R2 resection" may be allowed, after discussion with the study's principal investigator.
- Measurable disease by RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 and no medical contraindication to surgery.
- Adequately controlled blood pressure.
- Blood pressure ≤150/90 with or without antihypertensive medications at screening
- Adequate end-organ function (including bone marrow, coagulation, renal, liver and cardiac) 28 days prior to the study registration as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤1.5 x institutional upper limit of normal, unless attributed to Gilberts syndrome
- AST/ALT/Alk Phos ≤3 x institutional upper limit of normal
- INR ≤1.5 x institutional upper limit of normal
- creatinine within normal institutional limits OR
- creatinine clearance ≥30 mL/min per Cockcroft-Gault formulation
- The cycle 1 day 1 labs need to re-meet eligibility criteria for treatment
- Ability to swallow pills.
- Females must not be lactating or pregnant at baseline (as documented by a negative betahuman chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
- Note: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dosing).
- Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation.
- Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after.
Who cannot join
- Diagnosis of medullary thyroid carcinoma or anaplastic (undifferentiated) thyroid carcinoma.
- Radiographically identified following findings:
- intraluminal airway tumor
- complete carotid encasement/infiltration
- Active hemoptysis (bright red blood ≥ 1/2 teaspoon) or other uncontrolled bleeding within 21 days prior to the study registration.
- Arterial/venous thromboembolic events in the last 12 months Treatment within 30 days prior to study registration with anticoagulant or antiplatelet therapy, apart from aspirin 81 mg daily.
Show all 17Show fewer
- Prior radiotherapy to the neck.
- Prior treatment with lenvatinib or other VEGFR-directed therapy, including sorafenib.
- Known metastasis to central nervous system.
- Females who are pregnant or breastfeeding.
- If > 1 + proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1g/24 h will be ineligible.
- Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of study drug.
- Active infection requiring treatment.
- Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment.
- Prolongation of corrected QT interval (QTc) to > 480 ms as demonstrated by a repeated ECG or any clinically significant ECG abnormality
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib.
- Any medical or other condition that in the opinion of the investigators would preclude participant's participation in a clinical study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase 2 Study of Neoadjuvant Lenvatinib in Locally Advanced Invasive Thyroid Cancer
This research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC).
This research study involves a study drug called lenvatinib
Read the detailed description
This is a multicenter, phase II, open-label study examining the effect of neoadjuvant lenvatinib being given to patients with extrathyroidal differentiated thyroid cancer (DTC) prior to surgery to remove cancerous tumors (thyroidectomy).
- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
- This research study involves a study drug called lenvatinib.
- It is anticipated that 30 people will participate in the study.
The U.S. Food and Drug Administration (FDA) has not approved lenvatinib for the specific disease of extrathyroidal differentiated thyroid cancer (DTC) but it has been approved for other uses.
Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
- Conditions
- Differentiated Thyroid Cancer, Advanced Cancer
- Being tested
- LENVATINIB
- Keywords
- Differentiated Thyroid Cancer, Advanced Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LENVATINIBDrug
Also called Lenvima
Orally
| Study group | Role | What they receive |
|---|---|---|
| LENVATINIB | Experimental | Study procedures include screening for eligibility and study treatment, evaluations, and follow up visits
* Lenvatinib will be administered orally daily at a predetermined dose for 2, 4, or 6 cycles, dependent on response. 1 cycle is 28 days.
* Surgery per standard of care will follow lenvatinib treatment. Receives: Drug: LENVATINIB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall R0/R1 resection rate
Evaluate the overall R0/R1 resection rate, as defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive surgical margins (R1).
Measured: 112 Days
Secondary outcomes (6)
Resection rate of R0
Evaluate R0 resection rates in each of 4 pre-specified extrathyroidal anatomic target interfaces: R0=no cancer cells seen microscopically at the resection margin
Measured: 112 Days
Resection rate of R1
Evaluate R1 resection rates in each of 4 pre-specified extrathyroidal anatomic target interfaces: R1 cancer cells present microscopically at the resection margin (microscopic positive margin)
Measured: 112 Days
Change in Surgical complexity and morbidity score (SCMS)
The Thyroid Neck Group Morbidity Complexity Scoring and MGH/MEE-MSK-MD Anderson (MMM) Surgical Morbidity Complexity Score (SMCS) are incorporated, specifying on scale with 5 levels of complexity and morbidity of the surgery [mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)]. The surgical morbidity/complexity scores will be collected at enrollment, prior to surgery, and based on intraoperative findings.
The change in SCMS will be reported as the median SCMS value. Determined by structures requiring resection, the score takes into account preoperatively radiographically defined structures judged to be requiring resection with surgical complexity of the given resection/potential for complications, and expected patient morbidity/change of function from the resection.
Measured: 112 Days
Primary surgery response rate
Evaluate the response rate (RR) prior to primary surgery based on Response Evaluation Criteria in Solid Tumors version 1.1
Measured: 112 Days
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
CTCAE version 5
Measured: Up to 18 months
Unresectable to resectable conversion rate
The conversion rate will be summarized as frequency (%)
-- Determined by structures requiring resection, the RGS takes into account preoperatively radiographically defined structures judged to be requiring resection with surgical complexity of the given resection/potential for complications, and expected patient morbidity/change of function from the resection.
Measured: 112 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2020
- Study start9 Mar 2021
- Primary completion27 May 2025
- Study completion27 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Principal investigator, Gregory Randolph, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Gregory Randolph, MD, Principal investigator, Massachusetts Eye and Ear Infirmary (MEEI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04321954
- Sponsor's protocol ID
- 19-524
- Status last verified
- Jun 2026
- First submitted
- 24 Mar 2020
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Publications
Farlow JL, McCrary HC, Sipos JA, Phay JE, Konda B, Agrawal A. Neoadjuvant dabrafenib and trametinib for functional organ preservation in recurrent BRAF V600E-mutated papillary thyroid cancer. Oral Oncol. 2023 Dec;147:106625. doi: 10.1016/j.oraloncology.2023.106625. Epub 2023 Nov 8.
PubMed 37948895
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Neoadjuvant Lenvatinib in Locally Advanced Invasive Thyroid Cancer
- ClinicalTrials.gov ID
- NCT04321954
- Acronym / sponsor ID
- 19-524
- Conditions
- Differentiated Thyroid Cancer, Advanced Cancer
- Keywords
- Differentiated Thyroid Cancer, Advanced Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- 27 May 2025 (actual)
- Study completion
- 27 May 2026 (actual)
- First posted
- 25 Mar 2020 (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 research is being done to evaluate the safety and efficacy of neoadjuvant lenvatinib on surgical outcomes of patients with invasive extrathyroidal differentiated thyroid cancer (DTC).
This research study involves a study drug called lenvatinib
Detailed description
This is a multicenter, phase II, open-label study examining the effect of neoadjuvant lenvatinib being given to patients with extrathyroidal differentiated thyroid cancer (DTC) prior to surgery to remove cancerous tumors (thyroidectomy).
- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
- This research study involves a study drug called lenvatinib.
- It is anticipated that 30 people will participate in the study.
The U.S. Food and Drug Administration (FDA) has not approved lenvatinib for the specific disease of extrathyroidal differentiated thyroid cancer (DTC) but it has been approved for other uses.
Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LENVATINIB | Experimental | Drug: LENVATINIBStudy procedures include screening for eligibility and study treatment, evaluations, and follow up visits * Lenvatinib will be administered orally daily at a predetermined dose for 2, 4, or 6 cycles, dependent on response. 1 cycle is 28 days. * Surgery per standard of care will follow lenvatinib treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 18 years of age at the time of informed consent and willing and able to provide written informed consent for the trial.
- Adult participants who are either initially diagnosed with locally advanced thyroid neoplasm or have experienced persistent or recurrent thyroid and/or cervical nodal recurrent DTC (participants with M1 disease are allowed, AJCC 8th edition stage I-IVb)), including:
- Evidence of extrathyroidal extension and/or locally invasive disease and deemed at risk for R2 resection by treating team on clinical and/or fiberoptic examination and/or radiographic evaluation in the primary or recurrent setting. Evidence of "at risk for R2 resection" includes:
- Measurable disease by RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 and no medical contraindication to surgery.
Key exclusion criteria (17 listed)
- Diagnosis of medullary thyroid carcinoma or anaplastic (undifferentiated) thyroid carcinoma.
- Radiographically identified following findings:
- Active hemoptysis (bright red blood ≥ 1/2 teaspoon) or other uncontrolled bleeding within 21 days prior to the study registration.
- Arterial/venous thromboembolic events in the last 12 months Treatment within 30 days prior to study registration with anticoagulant or antiplatelet therapy, apart from aspirin 81 mg daily.
- Prior radiotherapy to the neck.
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 |
|---|---|---|
| LENVATINIBAlso: LenvimaOrally | Drug | LENVATINIB |
Primary outcome
Overall R0/R1 resection rate
Time frame: 112 Days
Evaluate the overall R0/R1 resection rate, as defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive surgical margins (R1).
6 secondary outcomes
Resection rate of R0
Time frame: 112 Days
Resection rate of R1
Time frame: 112 Days
Change in Surgical complexity and morbidity score (SCMS)
Time frame: 112 Days
Primary surgery response rate
Time frame: 112 Days
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
Time frame: Up to 18 months
Unresectable to resectable conversion rate
Time frame: 112 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Derived from this study: PubMed 37948895Farlow JL, McCrary HC, Sipos JA, Phay JE, Konda B, Agrawal A. Neoadjuvant dabrafenib and trametinib for functional organ preservation in recurrent BRAF V600E-mutated papillary thyroid cancer. Oral Oncol. 2023 Dec;147:106625. doi: 10.1016/j.oraloncology.2023.106625. Epub 2023 Nov 8.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Related trials for Differentiated Thyroid Cancer
RecruitingPhase 2
Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer
Differentiated Thyroid Carcinoma
Not yet recruitingObservational study
Serum Treg/Th17-Related Cytokines and Systemic Inflammatory Indices in Differentiated Thyroid Cancer
Differentiated Thyroid Cancer (DTC), Papillary Thyroid Carcinoma
RecruitingPhase 2
The Use of 124-I-PET/CT Whole Body and Lesional Dosimetry in Differentiated Thyroid Cancer
Thyroid Cancer
Not yet recruitingPhase 1
Study of ACC-1898 in Adult Participants With Advanced Solid Tumors
Hepatocellular Carcinoma, Renal Cell Carcinoma
Enrolling by invitationPhase 3
Long-Term Extension Study for Participants Previously Enrolled in an Exelixis-Sponsored Study
Cancer, Renal Cell Carcinoma (RCC)
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.
Gregory Randolph, MD principal investigator
Massachusetts Eye and Ear Infirmary (MEEI)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LENVATINIB in people with Differentiated Thyroid Cancer and Advanced Cancer, run by Massachusetts Eye and Ear Infirmary 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 34 inclusion and 17 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: finished, as of the sponsor's last update on 25 Jun 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall R0/R1 resection rate (time frame: 112 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04321954, which also lists 1 linked publication.
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 25 Jun 2026.