Lenvatinib 24 mg/Day Versus 10 mg/Day to Treat Symptomatic or Progressive Radioactive Iodine Resistant (RAIR) Differentiated Thyroid Cancer (DTC)

NCT07092514 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202508169
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, randomized phase II trial evaluates the dose delivery, tolerance, and efficacy of two dosing regimens of lenvatinib among patients with radioactive iodine resistant (RAIR) differentiated thyroid cancer (DTC).

Conditions

Thyroid Cancer; Cancer of the Thyroid

Keywords

Lenvatinib; Radioactive iodine resistant; Thyroid cancer

Outcome Measures

Primary Outcomes (1)

• Incidence rate of requiring a dose reduction of lenvatinib due to adverse event

  First 24 weeks of therapy

Secondary Outcomes (6)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 6 years)

• Incidence rate of requiring a dose interruption or delay of lenvatinib due to adverse event

  First 24 weeks of therapy

• Incidence rate of requiring discontinuation of lenvatinib due to adverse event

  First 24 weeks of therapy

• Daily dose intensity of lenvatinib

  First 24 weeks of therapy

• Number of patients with adverse events

  From start of treatment through 28 days after last dose of lenvatinib (estimated to be 13 months)

Study Arms (2)

Arm 1: Lenvatinib 10 mg/day

ACTIVE COMPARATOR

Lenvatinib 10 mg per day. Each cycle is 28 days.

Drug: Lenvatinib

Arm 2: Lenvatinib 24 mg/day

EXPERIMENTAL

Lenvatinib 24 mg per day. Each cycle is 28 days.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib is an oral drug which will be administered on an outpatient basis at a dose of 24 mg daily or 10 mg daily for an unlimited number of cycles.

Also known as: Lenvima

Arm 1: Lenvatinib 10 mg/day; Arm 2: Lenvatinib 24 mg/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed DTC, defined as papillary, follicular, or Hurthle Cell thyroid cancer. Papillary has several sub-types such as tall-cell and columnar cell, which are all allowed.
• Patient must have incurable RAIR DTC, defined as disease not amenable to cure by surgery AND meeting one or more of the following criteria:
• one or more sites of disease that do not take up RAI.
• disease progression on RAI (given within the last 12 months).
• receipt of cumulative dose of RAI of ≥ 600mCi.
• patient declines or is ineligible for surgery and/or RAI.
• Measurable or evaluable disease per RECIST 1.1.
• No more than 1 prior line of VEGF/VEGFR targeted therapy for DTC. Examples of VEGF/VEGFR therapies include sorafenib, pazopanib, vandetinib, axitinib, sunitinib, and cabozantinib, but others exist.
• Symptomatic (defined by usual standard of care clinical criteria) or progressive disease on most recent prior treatment (ex: surgery, RAI, or TKI/targeted therapy) by RECIST 1.1 over the last 16 months.
• At least 18 years of age.
• ECOG performance status ≤ 2.
• Screening blood pressure measurement \<140/90. Retesting is allowed.
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.0 K/cumm
• Platelets ≥ 100 K/cumm

You may not qualify if:

• Anaplastic, poorly differentiated/high-grade, and medullary thyroid cancers.
• Prior treatment with lenvatinib.
• 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.
• Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenvatinib or other agents used in the study.
• Use of concurrent medications that have a high risk for QTc prolongation. A 7 day washout period of the high-risk medication is required prior to the first dose of Lenvatinib if a patient discontinues the high risk medication for trial enrollment.
• 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.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 14 days of C1D1.
• 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.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
• Major surgery ≤ 14 days prior to C1D1; any surgical wound must be fully healed prior to C1D1.
• Measurable or evaluable disease per RECIST 1.1.
• Symptomatic (defined by usual standard of care clinical criteria) or progressive disease by RECIST 1.1 while on lenvatinib.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Brendan Knapp, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brendan Knapp, M.D.

CONTACT

314-362-5486; bjknapp@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients on Arm 1 can crossover to Arm 2 at the time of progression

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: July 30, 2025
• Study Start: October 14, 2025
• Primary Completion (Estimated): April 17, 2029
• Study Completion (Estimated): October 31, 2034
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 24 months following article publication.
• Access Criteria: Proposals may be submitted up to 24 months following article publication. Information regarding submitting proposals and accessing data may be submitted to jcley@wustl.edu.

Locations

US (1)