Phase II, Multicenter, Open-label, Single Arm Trial to Evaluate the Safety and Efficacy of Oral E7080 in Medullary and Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers, Stratified by Histology
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib (DTC Cohort)
- Conditions
- Thyroid Cancer
- Sponsor
- Eisai Inc.
- Enrollment
- 117
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief 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.
Detailed Description
This study contained 3 Phases: the Pretreatment Phase, the Treatment Phase, and the Extension Phase. The Pretreatment Phase lasted no longer than 28 days. Informed consent was obtained and protocol eligibility and disease characteristics were established prior to treatment. The Treatment Phase consisted of a Treatment Period and a Follow-up Period. The Treatment Period of the Treatment Phase began at the time that the first participant began study drug administration and ended at the time when all participants enrolled completed 8 cycles of treatment or discontinued study treatment prior to the eighth cycle (ie, time of data cutoff for the primary study analysis \[Primary Completion Date\]). All participants then entered the Extension Phase. The Extension Phase consisted of a Treatment Period and a Follow-up Period. The Extension Phase began immediately after the Treatment Phase ended and included all participants that were either still receiving treatment or in follow-up. The time of data cutoff for the primary study analysis occurred when all subjects in the study completed 8 cycles of treatment or discontinued study treatment prior to the eighth cycle.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
DTC cohort
This arm will enroll participants with radioiodine (131 I)-refractory/resistant differentiated thyroid cancer.
Intervention: Lenvatinib (DTC Cohort)
MTC cohort
This arm will enroll participants with medullary thyroid cancer.
Intervention: Lenvatinib (MTC Cohort)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months
ORR was the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 for target lesions using magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent imaging review (IIR). CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. ORR=CR+PR, was presented with 2-sided 95% confidence interval (CI) by the method of Clopper and Pearson.
Plasma Pharmacokinetics (PK): Steady State Area Under the Plasma Concentration Curve (AUC)
Time Frame: Cycle 1 Day 1 (predose and at 0.5 and 2 hours postdose), Cycle 1 Day 8 (predose), Cycle 2 Day 1 (predose and at 0.5 and 2 hours postdose), and Cycle 3 Day 1 (predose and at 2 hours postdose) (Cycle length= 28 days)
Up to 9 samples per participant were obtained at specific time points. Plasma concentrations of lenvatinib were analyzed using standard analysis methods. Due to the sparse PK sampling in this study, the data were pooled with data from other Phase 1 studies conducted in participants with solid tumors for PK model development and covariate analysis. Individual exposure (steady state AUC) to lenvatinib in MTC and DTC subjects in this study was derived based on the individual predicted steady state AUC from the final PK model. Only data for participants taking 24 mg lenvatinib daily were reported (participants taking 20 mg lenvatinib daily were not included in this data set).
Secondary Outcomes
- Change From Baseline in Free Thyroid Stimulating Hormone (TSH)(Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Percent Change From Baseline in Concentrations of Thyroglobulin (DTC Only)(Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 19, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Change From Baseline in Concentrations of M-30 Neo-Antigen(Cycle 1 (Day 8), Cycle 2 (Days 1, 8 & 15), Cycles 3, 4, 5, 6, 7, 8, 9, 11 & 13 (Day 1) and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Progression Free Survival (PFS) Assessed as Per IIR(From date of treatment start until date of progressive disease or death from any cause, assessed up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months)
- Change From Baseline in Concentrations of Cytochrome C (CytoC)(Cycle 1 (Day 8), Cycle 2 (Days 1, 8 and 15), Cycles 3, 4, 5, 6, 7, 8, 9, 11, & 13 (Day 1), and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Change From Baseline in Concentrations of Activated Caspase 3/7 (Casp 3/7)(Cycle 1 (Day 8), Cycle 2 (Days 1, 8, & 15), Cycles 3, 4, 5, 6, 7, 8, 9, 11, & 13 (Day 1) and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Time to Response (TTR) Assessed as Per IIR(From date of treatment start until date of first CR or PR, assessed up to data cutoff date 11 April 2011)
- Overall Survival (OS)(From date of treatment start until date of death from any cause, assessed up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months)
- Disease Control Rate (DCR) Assessed as Per IIR(From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months)
- Change From Baseline in Free Thyroxine (T4)(Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Duration of Response (DoR) Assessed as Per Independent Imaging Reviewers (IIR)(From date of the first CR or PR until the date of first documentation of disease progression or date of death, assessed up to data cutoff date 11 April 2011)
- Clinical Benefit Rate (CBR) Assessed as Per IIR(From date of treatment start until disease progression, development of unacceptable toxicity, withdrawal of consent, participant's choice to stop study treatment, or up to data cutoff date 11 April 2011, for up to approximately 2 years 5 months)
- Percent Change From Baseline in Concentrations of Calcitonin (MTC Only)(Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Percent Change From Baseline in Concentrations of Carcinoembryonic Antigen (CEA) (MTC Only)(Day 1 or within 72 hours prior to Day 1 of Cycles 2 to 20, and Final Visit, up to data cutoff date 11 April 2011 (Cycle length= 28 days))
- Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib(For each participant, from the first dose till 30 days after the last dose of study treatment (up to approximately 10 years 4 months))