Columnar Cell Variant Thyroid Gland Papillary CarcinomaPhase 2NCT02973997
Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC)
A Phase 2 study testing Laboratory Biomarker Analysis, Lenvatinib and Lenvatinib Mesylate in people with Columnar Cell Variant Thyroid Gland Papillary Carcinoma and Follicular Variant Thyroid Gland Papillary Carcinoma, run by Academic and Community Cancer Research United at 7 sites in United States.
Trial summary
This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with differentiated thyroid cancer that has spread to other places in the body or has come back and cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Columnar Cell Variant Thyroid Gland Papillary Carcinoma, Follicular Variant Thyroid Gland Papillary Carcinoma, Metastatic Thyroid Gland Follicular Carcinoma
- What is being tested?
- Laboratory Biomarker Analysis, Lenvatinib and Lenvatinib Mesylate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 7 sitesUnited States
- Study dates
- 7 Feb 2018to 8 Oct 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Locally recurrent and unresectable and/or distant metastatic differentiated thyroid cancer (DTC), histologically or cytologically confirmed; the diagnosis of DTC includes the following subtypes: papillary thyroid cancer (PTC) (including but not limited to variants such as follicular variant, tall cell, columnar cell, Hurthle cell variant of papillary carcinoma, and poorly differentiated), follicular thyroid cancer (FTC), including insular variant, Hurthle cell carcinoma and poorly differentiated thyroid cancer
- Measurable disease meeting the following criteria:
- At least 1 lesion of >= 1.0 cm in the longest diameter for a non-lymph node or >= 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI); if there is only one target lesion and it is a non-lymph node, it should have a longest diameter of >= 1.5 cm
- Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
- For cohort 1 only: evidence of disease progression =< 14 months prior to registration according to RECIST 1.1, as confirmed by the site study principal investigator (PI)
- For cohort 2 only: progressive disease (PD) on lenvatinib per RECIST 1.1 =< 60 days prior to registration, as confirmed by the site study PI; patients need to have documented imaging and measurement of RECIST target lesions within 30 days of starting pembrolizumab
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- Radioiodine (RAI)-resistant disease as defined by one or more of the following criteria:
- One or more measurable lesions that do not demonstrate RAI uptake
- One or more measurable lesions progressive by RECIST 1.1 =< 14 months of prior RAI therapy
- One or more measurable lesions present after cumulative RAI dose of >= 600 mCi
- One or more measurable lesions that are fludeoxyglucose F-18 (FDG)-avid (> 5 standardized uptake value [SUV]), if positron emission tomography (PET)/CT scan performed; these lesions may also be RAI-avid
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Absolute neutrophil count (ANC) >= 1,500 /mcL (obtained =< 30 days prior to registration)
- Platelets >= 100,000 / mcL (obtained =< 30 days prior to registration)
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin dependency (=< 7 days prior to registration) (obtained =< 30 days prior to registration)
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (obtained =< 30 days prior to registration)
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (obtained =< 30 days prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (obtained =< 30 days prior to registration)
- Albumin >= 2.5 mg/dL (obtained =< 30 days prior to registration)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained =< 30 days prior to registration)
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained =< 30 days prior to registration)
- Adequately controlled blood pressure with or without antihypertensive medications defined as blood pressure (BP) < 150/90 mmHg at screening
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Ability to complete patient medication and blood pressure diaries by themselves or with assistance
- Willing and able to provide informed written consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Note: during the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
- Willing to provide tissue and blood samples for correlative research purposes
Who cannot join
- Cohort 1 only: prior treatment with previous VEGFR active multikinase inhibitor
- Cohort 2 only: discontinued lenvatinib due to toxicity
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Female subjects of childbearing potential: unwilling or unable to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; NOTE: subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects: unwilling or unable to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
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- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive (HIV 1/2 antibodies) and currently receiving antiretroviral therapy
- Currently participating and receiving study therapy (except lenvatinib for patients in cohort 2) or has participated in a study of an investigational agent and received study therapy within 4 weeks prior to registration
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy =< 7 days prior to the first dose of trial treatment
- Known history of active TB (Bacillus tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients
- Prior anti-cancer monoclonal antibody (mAb) =< 4 weeks prior to registration or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered >= 4 weeks prior to registration
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 (except lenvatinib for patients in cohort 2) or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
- NOTE:
- Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to registration, as deemed by treating investigator or site PI
- Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; NOTE: subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for >= 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); NOTE: replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Known history of, or any evidence of active, non-infectious pneumonitis that required steroids
- Active infection requiring systemic therapy
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
- Received a live vaccine =< 30 days of planned start of study therapy; NOTE: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
- Proteinuria > 1+ on dipstick urinalysis; patients with > 1+ proteinuria on dipstick urinalysis will undergo 24-hour urine collection for quantitative assessment; NOTE: patients with > 1 g/24 hours will be ineligible
- Clinically significant gastrointestinal malabsorption syndrome
- New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months; ejection fraction (EF) by multi-gated acquisition (MUGA) or echo should not be less than the institutional lower limit of normal
- Corrected QT (QTc) prolongation > 480 msec, as calculated by either the Bazett or Fridericia formula, as per institutional standard
- Active hemoptysis (bright red blood > 1 teaspoon on more than one occasion) =< 3 weeks prior to registration
- Cohort 2 only: more than one prior treatment with VEGFR active multikinase inhibitor prior to original start of lenvatinib
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
University of Colorado Hospital
Aurora, Colorado, 80045
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
M D Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers: A Phase II Study
This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with differentiated thyroid cancer that has spread to other places in the body or has come back and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
PRIMARY OBJECTIVES:
- To investigate the clinical efficacy, as indicated by the rate of complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, of combination therapy with pembrolizumab and lenvatinib in lenvatinib-naive patients with progressive radioiodine-refractory differentiated thyroid cancers (DTC). (Cohort 1) II. To determine the overall response rate (ORR) by the addition of pembrolizumab to patients with radioiodine-refractory DTC who have progressive disease on lenvatinib alone. (Cohort 2)
SECONDARY OBJECTIVES:
- To determine the safety profile and toxicity of combination therapy with pembrolizumab and lenvatinib in patients with progressive DTC. (Cohort 1 and cohort 2) II. To determine progression-free survival (PFS) and overall survival (OS). (Cohort 1 and cohort 2)
CORRELATIVE RESEARCH OBJECTIVES:
- To correlate tumor response (RECIST 1.1) with pretreatment frequency of CD8+ T cells in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) II. To correlate tumor response (RECIST 1.1) with pretreatment PD-L1 and PD-L2 levels in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) III. To correlate tumor response (RECIST 1.1) with pretreatment frequency of lymphocytes expressing CD3, CD4, PD-1, FoxP3, or CD20, and of CD163+ macrophages. (Cohort 1 and cohort 2) IV. To correlate tumor response (RECIST 1.1) with the phenotype and frequency of key leukocyte subsets (i.e., PD-1+ T cells, regulatory T cells [Tregs], myeloid subsets) in the peripheral blood before, at 6 and 18 weeks on therapy, and at 54 weeks (study completion), progressive disease (PD), or study withdrawal. (Cohort 1) V. To correlate tumor response (RECIST 1.1) with PD-1+ T cell functional capacity. (Cohort 1) VI. To correlate tumor response (RECIST 1.1) with serum anti-thyroglobulin antibody levels assessed before, and at 18 weeks on therapy. (Cohort 1 and 2) VII. To correlate tumor response (RECIST 1.1) with tumor mutation status. (Cohort 1) VIII. To broadly investigate mechanisms of response and resistance to combination therapy, gene expression profiles will be generated from frozen biopsies for analysis by ribonucleic acid-sequencing (RNA-Seq). (Cohort 1)
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.
After completion of study treatment, patients are followed up every 3 months for up to 3 years.
- Conditions
- Columnar Cell Variant Thyroid Gland Papillary Carcinoma, Follicular Variant Thyroid Gland Papillary Carcinoma, Metastatic Thyroid Gland Follicular Carcinoma, Metastatic Thyroid Gland Papillary Carcinoma, Poorly Differentiated Thyroid Gland Carcinoma, Recurrent Differentiated Thyroid Gland Carcinoma
- Being tested
- Laboratory Biomarker Analysis, Lenvatinib, Lenvatinib Mesylate, Pembrolizumab
- Medical subject headings
- Adenocarcinoma, Follicular, Thyroid Cancer, Papillary, Thyroid cancer, Hurthle cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
LenvatinibDrug
Also called E7080, ER-203492-00, Multi-Kinase Inhibitor E7080
Given PO
Lenvatinib MesylateDrug
Also called 4-[3-Chloro-4-(N''-cyclopropylureido)phenoxy]7-methoxyquinoline-6-carboxamide Mesylate, E7080, Lenvima, Multi-Kinase Inhibitor E7080
Given PO
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (lenvatinib, pembrolizumab) | Experimental | Patients receive lenvatinib PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles. Receives: Other: Laboratory Biomarker Analysis; Drug: Lenvatinib; Drug: Lenvatinib Mesylate; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate (Cohort 1)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will use a one-stage binomial design.
Measured: 26 months
Confirmed Response Rate (Cohort 2)
Assessed by RECIST 1.1. Will use a 2-stage Simon Optimal MinMax design.
Measured: 27 months
Secondary outcomes (3)
Number of Patients Experiencing Grade 3+ Adverse Events
Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. All patients that have initiated treatment will be considered evaluable for assessing adverse events. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. Only the grade 2+ adverse events will be assessed, regardless of relationship to the study treatment.
Measured: 27 months
Progression Free Survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan-Meier.
Measured: 12 months
Overall Survival (OS)
The distribution of survival at 12 months will be estimated using the method of Kaplan-Meier.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2016 (estimated)
- Study start7 Feb 2018
- Primary completion15 Aug 2022
- Study completion8 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Columnar Cell Variant Thyroid Gland Papillary CarcinomaStudies 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
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academic and Community Cancer Research United
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Bryan R Haugen, Principal investigator, Academic and Community Cancer Research United
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02973997
- Sponsor's protocol ID
- ACCRU-ITOG-1504
- Other IDs
- NCI-2016-01752, ACCRU-ITOG-1504, P30CA015083
- Status last verified
- Aug 2025
- First submitted
- 23 Nov 2016
- Last updated
- 29 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Baste N, Mora M, Grau JJ. Emerging systemic antitarget treatment for differentiated thyroid carcinoma. Curr Opin Oncol. 2021 May 1;33(3):184-195. doi: 10.1097/CCO.0000000000000727.
PubMed 33720068
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Targeted Therapy With Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers: A Phase II Study
- ClinicalTrials.gov ID
- NCT02973997
- Acronym / sponsor ID
- ACCRU-ITOG-1504
- Conditions
- Columnar Cell Variant Thyroid Gland Papillary Carcinoma, Follicular Variant Thyroid Gland Papillary Carcinoma, Metastatic Thyroid Gland Follicular Carcinoma, Metastatic Thyroid Gland Papillary Carcinoma, Poorly Differentiated Thyroid Gland Carcinoma, Recurrent Differentiated Thyroid Gland Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Academic and Community Cancer Research UnitedUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 15 Aug 2022 (actual)
- Study completion
- 8 Oct 2023 (actual)
- First posted
- 28 Nov 2016 (estimated)
- Results
- Posted 24 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well pembrolizumab and lenvatinib work in treating patients with differentiated thyroid cancer that has spread to other places in the body or has come back and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES:
- To investigate the clinical efficacy, as indicated by the rate of complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, of combination therapy with pembrolizumab and lenvatinib in lenvatinib-naive patients with progressive radioiodine-refractory differentiated thyroid cancers (DTC). (Cohort 1) II. To determine the overall response rate (ORR) by the addition of pembrolizumab to patients with radioiodine-refractory DTC who have progressive disease on lenvatinib alone. (Cohort 2)
SECONDARY OBJECTIVES:
- To determine the safety profile and toxicity of combination therapy with pembrolizumab and lenvatinib in patients with progressive DTC. (Cohort 1 and cohort 2) II. To determine progression-free survival (PFS) and overall survival (OS). (Cohort 1 and cohort 2)
CORRELATIVE RESEARCH OBJECTIVES:
- To correlate tumor response (RECIST 1.1) with pretreatment frequency of CD8+ T cells in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) II. To correlate tumor response (RECIST 1.1) with pretreatment PD-L1 and PD-L2 levels in the primary and/or metastatic tumor. (Cohort 1 and cohort 2) III. To correlate tumor response (RECIST 1.1) with pretreatment frequency of lymphocytes expressing CD3, CD4, PD-1, FoxP3, or CD20, and of CD163+ macrophages. (Cohort 1 and cohort 2) IV. To correlate tumor response (RECIST 1.1) with the phenotype and frequency of key leukocyte subsets (i.e., PD-1+ T cells, regulatory T cells [Tregs], myeloid subsets) in the peripheral blood before, at 6 and 18 weeks on therapy, and at 54 weeks (study completion), progressive disease (PD), or study withdrawal. (Cohort 1) V. To correlate tumor response (RECIST 1.1) with PD-1+ T cell functional capacity. (Cohort 1) VI. To correlate tumor response (RECIST 1.1) with serum anti-thyroglobulin antibody levels assessed before, and at 18 weeks on therapy. (Cohort 1 and 2) VII. To correlate tumor response (RECIST 1.1) with tumor mutation status. (Cohort 1) VIII. To broadly investigate mechanisms of response and resistance to combination therapy, gene expression profiles will be generated from frozen biopsies for analysis by ribonucleic acid-sequencing (RNA-Seq). (Cohort 1)
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles.
After completion of study treatment, patients are followed up every 3 months for up to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lenvatinib, pembrolizumab) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Lenvatinib, Drug: Lenvatinib Mesylate, Biological: PembrolizumabPatients receive lenvatinib PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 19 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue treatment for up to 35 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Locally recurrent and unresectable and/or distant metastatic differentiated thyroid cancer (DTC), histologically or cytologically confirmed; the diagnosis of DTC includes the following subtypes: papillary thyroid cancer (PTC) (including but not limited to variants such as follicular variant, tall cell, columnar cell, Hurthle cell variant of papillary carcinoma, and poorly differentiated), follicular thyroid cancer (FTC), including insular variant, Hurthle cell carcinoma and poorly differentiated thyroid cancer
- Measurable disease meeting the following criteria:
- For cohort 1 only: evidence of disease progression =< 14 months prior to registration according to RECIST 1.1, as confirmed by the site study principal investigator (PI)
- For cohort 2 only: progressive disease (PD) on lenvatinib per RECIST 1.1 =< 60 days prior to registration, as confirmed by the site study PI; patients need to have documented imaging and measurement of RECIST target lesions within 30 days of starting pembrolizumab
- Radioiodine (RAI)-resistant disease as defined by one or more of the following criteria:
Key exclusion criteria (32 listed)
- Cohort 1 only: prior treatment with previous VEGFR active multikinase inhibitor
- Cohort 2 only: discontinued lenvatinib due to toxicity
- Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Female subjects of childbearing potential: unwilling or unable to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; NOTE: subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects: unwilling or unable to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (lenvatinib, pembrolizumab) |
| LenvatinibAlso: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080Given PO | Drug | Treatment (lenvatinib, pembrolizumab) |
| Lenvatinib MesylateAlso: 4-[3-Chloro-4-(N''-cyclopropylureido)phenoxy]7-methoxyquinoline-6-carboxamide Mesylate, E7080, Lenvima, Multi-Kinase Inhibitor E7080Given PO | Drug | Treatment (lenvatinib, pembrolizumab) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (lenvatinib, pembrolizumab) |
Primary outcome
Complete Response Rate (Cohort 1)
Time frame: 26 months
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will use a one-stage binomial design.
Confirmed Response Rate (Cohort 2)
Time frame: 27 months
Assessed by RECIST 1.1. Will use a 2-stage Simon Optimal MinMax design.
3 secondary outcomes
Number of Patients Experiencing Grade 3+ Adverse Events
Time frame: 27 months
Progression Free Survival (PFS)
Time frame: 12 months
Overall Survival (OS)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33720068Baste N, Mora M, Grau JJ. Emerging systemic antitarget treatment for differentiated thyroid carcinoma. Curr Opin Oncol. 2021 May 1;33(3):184-195. doi: 10.1097/CCO.0000000000000727.
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.
Bryan R Haugen principal investigator
Academic and Community Cancer Research United
7 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 Laboratory Biomarker Analysis, Lenvatinib and Lenvatinib Mesylate in people with Columnar Cell Variant Thyroid Gland Papillary Carcinoma and Follicular Variant Thyroid Gland Papillary Carcinoma, run by Academic and Community Cancer Research United at 7 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 28 inclusion and 32 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 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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?
Yes. Results are posted in the registry (first posted 24 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Response Rate (Cohort 1) (time frame: 26 months). The study lists 2 primary outcomes in all. 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 NCT02973997, 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 29 Aug 2025; AzTrials last refreshed its copy on 26 Oct 2026.