A Study of E7080 in Subjects With Advanced Thyroid Cancer

Study Overview
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Brief Summary
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This study is to evaluate the safety, efficacy, and pharmacokinetics of E7080 when orally administered once daily (QD) in subjects with advanced thyroid cancer.

Official Title
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A Phase 2 Study of E7080 in Subjects With Advanced Thyroid Cancer

Conditions
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Thyroid Cancer

Intervention / Treatment
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* Drug: E7080 capsule


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histologically or clinically diagnosed with thyroid cancer Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-2 Adequate laboratory values/organ function tests Exclusion criteria Participants with following complication or disease history Brain metastasis Systemic severe infection Significant cardiovascular impairment QTc greater than 480 milliseconds Active hemoptysis Bleeding or thrombotic disorders Having greater than 1+ proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of E7080 Major surgery within 3 weeks before enrollment With co-existing effusion requiring drainage

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E7080<br> | Drug: E7080 capsule<br>* E7080 is administered as continuous once daily dosing in an uncontrolled manner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Only TEAEs are included in the summary. For detailed list of adverse events (AEs), see the AE section. For each participant, only one TEAE in the same category was counted and for multiple TEAEs with different Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grades, only the event with the highest grade was reported. All AEs were graded using CTCAE v 4.0, except for alopecia and infertility. | Screening visit to 30 days after the last dose of study drug, or assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the time from (1) the date of randomization to the date of first documentation of disease progression based on Investigator and Independent Review Committee assessments according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), or (2) death, whichever came first. Disease progression for the MTC group was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors. Disease progression per RECIST v1.1 was defined as at least a 20 percent (%) relative increase and 5 millimeter (mm) absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. Summarized by the Kaplan-Meier method using median time with 95% confidence interval (CI). | From first date of study treatment until progression of disease or date of death from any cause, whichever comes first, assessed up to 34 months | 
| Overall Survival (OS) | OS was defined as the time from the date of first dose of study treatment to the date of death from any cause. If death was not observed for a participant, the survival time was censored at the date the participant was last known alive or the data cutoff date (whichever occurred first). Summarized by the Kaplan-Meier method using median time with 95% CI. | From study start until date of death from any cause, assessed up to 34 months | 
| Best Overall Response (BOR) | BOR was defined as the best response observed between the time of first dose and the study completion, assessed by either of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Tumor assessment was performed by the investigator using RECIST 1.1. The CR and PR were determined only when these responses met each criterion even after 28 days from the time observed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as greater than or equal to 7 weeks for DTC and MTC, greater than or equal to 3 weeks for ATC. | Date of first dose of study treatment to CR, PR, SD, PD, or NE, assessed up to 34 months | 
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants who had BOR of CR or PR. Tumor assessment was performed by the investigator using RECIST 1.1. ORR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution. | Date of CR or PR to date of PD or death (whichever was first), assessed up to 34 months | 
| Disease Control Rate (DCR) | The DCR was defined as the percentage of participants who had BOR of CR, PR, or SD. Tumor assessment was performed by the investigator using RECIST 1.1. DCR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution. | Date of CR, PR, or SD to date of PD or death (whichever was first), assessed up to 34 months | 
| Clinical Benefit Rate (CBR) | The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (dSD). Tumor assessment was performed by the investigator using RECIST 1.1. Durable stable disease was defined as SD lasting greater than or equal to 23 weeks for DTC and MTC, greater than or equal to 11 weeks for ATC. A 95% CI was calculated using exact method of binomial distribution. | Date of CR, PR, or dSD to date of PD or death (whichever was first), assessed up to 34 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroid cancer