Phase 2
N=117
Evaluating the Safety and Efficacy of Oral Lenvatinib in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology
Thyroid Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00784303 ↗Enrolled (actual)
117
Serious AEs
63.2%
Results posted
Aug 2019
Primary outcome: Primary: Objective Response Rate (ORR) — 50.0; 35.6 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Lenvatinib (DTC Cohort) (Drug); Lenvatinib (MTC Cohort) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eisai Inc.
- Primary completion
- Apr 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate (ORR) |
50.0; 35.6 | — |
| PRIMARY Plasma Pharmacokinetics (PK): Steady State Area Under the Plasma Concentration Curve (AUC) |
3840; 3350 | — |
| SECONDARY Change From Baseline in Free Thyroxine (T4) |
-3.80; -0.46; -0.86; -0.92; -1.00; -1.05 | — |
| SECONDARY Change From Baseline in Free Thyroid Stimulating Hormone (TSH) |
2.8030; 0.4779; 4.1585; 0.5161; 5.5788; 0.6296 | — |
| SECONDARY Percent Change From Baseline in Concentrations of Thyroglobulin (DTC Only) |
-62.21; -77.80; -79.25; -76.00; -20.36; -73.38 | — |
| SECONDARY Percent Change From Baseline in Concentrations of Calcitonin (MTC Only) |
-42.27; -48.11; -44.54; -49.97; -41.73; -38.18 | — |
| SECONDARY Percent Change From Baseline in Concentrations of Carcinoembryonic Antigen (CEA) (MTC Only) |
-26.07; -37.68; -41.49; -44.62; -41.91; -41.39 | — |
| SECONDARY Change From Baseline in Concentrations of Cytochrome C (CytoC) |
155.57; 502.84; 1679.40; -218.45; 374.46; -215.50 | — |
| SECONDARY Change From Baseline in Concentrations of M-30 Neo-Antigen |
-5.22; 46.32; -77.80; -26.41; -49.33; 35.30 | — |
| SECONDARY Change From Baseline in Concentrations of Activated Caspase 3/7 (Casp 3/7) |
NA; 0.0030; 0.0080; NA; 0.0039; 0.0110 | — |
| SECONDARY Duration of Response (DoR) Assessed as Per Independent Imaging Reviewers (IIR) |
12.7; NA | — |
| SECONDARY Disease Control Rate (DCR) Assessed as Per IIR |
93.1; 79.7 | — |
| SECONDARY Clinical Benefit Rate (CBR) Assessed as Per IIR |
77.6; 64.4 | — |
| SECONDARY Time to Response (TTR) Assessed as Per IIR |
3.6; 3.5 | — |
| SECONDARY Progression Free Survival (PFS) Assessed as Per IIR |
12.6; 9.0 | — |
| SECONDARY Overall Survival (OS) |
27.7; 16.6 | — |
| SECONDARY Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib |
58; 59; 32; 42 | — |
Summary
The purpose of this study is to determine the safety and efficacy of oral lenvatinib in participants with medullary thyroid cancer (MTC) or radioiodine (131 I)-refractory/resistant differentiated thyroid cancer (DTC), unresectable differentiated thyroid cancers, stratified by Histology.
Eligibility Criteria
Inclusion criteria
- Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC) or differentiated thyroid cancer (DTC).
- Measurable disease meeting the following criterion:
- At least one lesion (greater than or equal to 1.5 cm in longest diameter for non-lymph nodes and greater than or equal to 2.0 cm in longest diameter for lymph nodes) which is serially and accurately measurable according to modified response evaluation criteria in solid tumours (RECIST) using either computed tomography (CT) or magnetic resonance imaging (MRI).
- Lesions that have had electron beam radiotherapy must show evidence of progressive disease based on modified RECIST to be deemed a target lesion.
- Evidence of disease progression by RECIST using site assessment of CT/MRI scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry.
- DTC must be 131-I refractory/resistant: never demonstrated 131-I uptake, progression despite 131-I uptake, or cumulative dose of 131-I of greater than 600 millicurie (mCi) (last dose given at least 6 months prior to study entry).
- Well controlled blood pressure prior to study entry.
Exclusion criteria
- Anaplastic thyroid carcinoma, thyroid lymphoma, mesenchymal tumors of the thyroid, metastases to the thyroid.
- Brain or leptomeningeal metastases.
- Significant cardiovascular impairment (history of congestive heart failure, New York Heart Association [NYHA] Class II, unstable angina or myocardial infarction within 6 months of study start, or serious cardiac arrhythmia).
- Marked baseline prolongation of QT/corrected QT (QTc) interval.
- Proteinuria greater than 1+ or greater than 30 mg in dipstick testing.
- Active hemoptysis (bright red blood of at least one-half teaspoon) in the 28 days prior to study entry.
Data sourced from ClinicalTrials.gov (NCT00784303). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.