A Study of E7080 in Subjects With Advanced Thyroid Cancer

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01728623

Enrollment

Registered

2012-11-20

Start date

2012-09-03

Completion date

2015-10-01

Last updated

2020-08-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Thyroid Cancer

Keywords

Thyroid cancer

Brief summary

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

Interventions

DRUGE7080 capsule

E7080 is administered as continuous once daily dosing in an uncontrolled manner

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Histologically or clinically diagnosed with thyroid cancer 2. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-2 3. Adequate laboratory values/organ function tests

Exclusion criteria

Participants with following complication or disease history 1. Brain metastasis 2. Systemic severe infection 3. Significant cardiovascular impairment 4. QTc greater than 480 milliseconds 5. Active hemoptysis 6. Bleeding or thrombotic disorders 7. Having greater than 1+ proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria 8. Gastrointestinal malabsorption or any other condition in the opinion of the investigator that might affect the absorption of E7080 9. Major surgery within 3 weeks before enrollment 10. With co-existing effusion requiring drainage

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	Screening visit to 30 days after the last dose of study drug, or assessed up to 3 years	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.

Secondary

Measure	Time frame	Description
Progression-free Survival (PFS)	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	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).
Overall Survival (OS)	From study start until date of death from any cause, assessed up to 34 months	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.
Best Overall Response (BOR)	Date of first dose of study treatment to CR, PR, SD, PD, or NE, assessed up to 34 months	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.
Objective Response Rate (ORR)	Date of CR or PR to date of PD or death (whichever was first), assessed up to 34 months	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.
Disease Control Rate (DCR)	Date of CR, PR, or SD to date of PD or death (whichever was first), assessed up to 34 months	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.
Clinical Benefit Rate (CBR)	Date of CR, PR, or dSD to date of PD or death (whichever was first), assessed up to 34 months	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.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
Lenvatinib (Arm 1) Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.	25
Lenvatinib (Arm 2) Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.	9
Lenvatinib (Arm 3) Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.	17
Total	51

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Disease progression	26
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Lenvatinib (Arm 1)	Lenvatinib (Arm 2)	Lenvatinib (Arm 3)	Total
Age, Continuous	57.1 years STANDARD_DEVIATION 12.34	60.6 years STANDARD_DEVIATION 13.7	63.4 years STANDARD_DEVIATION 11.4	59.8 years STANDARD_DEVIATION 12.36
Sex: Female, Male Female	16 Participants	3 Participants	11 Participants	30 Participants
Sex: Female, Male Male	9 Participants	6 Participants	6 Participants	21 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	4 / 51
other Total, other adverse events	51 / 51
serious Total, serious adverse events	27 / 51

Outcome results

Primary

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.

Time frame: Screening visit to 30 days after the last dose of study drug, or assessed up to 3 years

Population: Safety population included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation.

Arm	Measure	Group	Value (NUMBER)
Arm 4: Lenvatinib (DTC, MTC, ATC)	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAEs	100.0 Percentage of participants
Arm 4: Lenvatinib (DTC, MTC, ATC)	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	CTCAE Grade 3 or 4 TEAEs	82.4 Percentage of participants
Arm 4: Lenvatinib (DTC, MTC, ATC)	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	Serious TEAEs	52.9 Percentage of participants
Arm 4: Lenvatinib (DTC, MTC, ATC)	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAEs leading to study drug withdrawal	2.0 Percentage of participants
Arm 4: Lenvatinib (DTC, MTC, ATC)	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAEs leading to study drug reduction	96.1 Percentage of participants
Arm 4: Lenvatinib (DTC, MTC, ATC)	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAEs leading to study drug interruption	66.7 Percentage of participants

Secondary

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.

Time frame: Date of first dose of study treatment to CR, PR, SD, PD, or NE, assessed up to 34 months