Brief Summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study to compare the progression free survival, overall response rate (ORR) and safety of participants treated with lenvatinib 24 mg by continuous once daily oral dosing versus placebo. The study is conducted in 3 phases: a Prerandomization Phase (screening and baseline period), a Randomization Phase (double-blind treatment period), and an Extension Phase (Optional Open Label (OOL) Lenvatinib Treatment Period and a follow-up period).
Brief Title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)
Detailed Description
Randomization Phase: Participants will receive blinded study drug (lenvatinib/placebo) in 2:1 ratio until documentation of disease progression (confirmed by independent imaging review), development of unacceptable toxicity, or withdrawal of consent. After having completed the primary analysis, subjects treated with lenvatinib who have not experienced disease progression may request to continue open label lenvatinib at the same dose, according to the clinical judgment of the investigator. Participants who discontinue treatment for any reason other than disease progression will be followed in the Randomization Phase until disease progression or start of another anticancer treatment; these participants then enter the Extension Phase for survival follow-up. Extension Phase: Participants in the placebo arm who have disease progression confirmed by IIR could request to enter the OOL Lenvatinib Treatment Period and receive lenvatinib treatment. Participants will receive lenvatinib treatment until disease progression (investigator's assessment), development of intolerable toxicity, or withdrawal of consent. Participants who had disease progression during the Randomization Phase and did not enter the OOL Lenvatinib Treatment Period and all participants who discontinued lenvatinib treatment in the OOL Lenvatinib Treatment Period will enter the follow-up period. Participants will be followed for survival, and all anticancer treatments will be recorded until the time of death.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Thyroid Cancer
Eligibility Criteria
Inclusion criteria:
1. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC).
2. Measurable disease according to (RECIST 1.1) and confirmed by central radiographic review.
3. 131 I-refractory/resistant disease.
4. Evidence of disease progression within 12 months prior to signing informed consent (+1 month screening window).
5. Prior treatment with 0 or 1 vascular endothelial growth-factor (VEGF) or vascular endothelial growth-factor receptors (VEGFR) targeted therapy.
6. Adequate renal, liver, bone marrow, and blood coagulation function, as defined in the protocol.
Exclusion criteria:
1. Anaplastic or medullary carcinoma of the thyroid
2. 2 or more prior VEGF/ VEGFR-targeted therapies
3. Received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug.
Inclusion criteria for OOL Lenvatinib Treatment Period :
Participants were eligible for lenvatinib treatment in the OOL Lenvatinib Treatment Period if the met the following criteria:
1. Placebo-treated participants in the Randomization Phase who had progressive disease (PD) confirmed by IIR, and who requested treatment with lenvatinib.
2. Participants who continued to satisfy specified inclusion and exclusion criteria as presented in the study protocol.
3. Participants with maximum interval between the day of confirmation of PD by IIR and Cycle 1/Day 1 of the OOL Lenvatinib Treatment Period of less than or equal to 3 months.
4. No systemic anticancer treatment during the interval between the day of confirmation of PD by the IIR and Cycle 1/Day 1 of the OOL Lenvatinib Treatment Period.
1. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC).
2. Measurable disease according to (RECIST 1.1) and confirmed by central radiographic review.
3. 131 I-refractory/resistant disease.
4. Evidence of disease progression within 12 months prior to signing informed consent (+1 month screening window).
5. Prior treatment with 0 or 1 vascular endothelial growth-factor (VEGF) or vascular endothelial growth-factor receptors (VEGFR) targeted therapy.
6. Adequate renal, liver, bone marrow, and blood coagulation function, as defined in the protocol.
Exclusion criteria:
1. Anaplastic or medullary carcinoma of the thyroid
2. 2 or more prior VEGF/ VEGFR-targeted therapies
3. Received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug.
Inclusion criteria for OOL Lenvatinib Treatment Period :
Participants were eligible for lenvatinib treatment in the OOL Lenvatinib Treatment Period if the met the following criteria:
1. Placebo-treated participants in the Randomization Phase who had progressive disease (PD) confirmed by IIR, and who requested treatment with lenvatinib.
2. Participants who continued to satisfy specified inclusion and exclusion criteria as presented in the study protocol.
3. Participants with maximum interval between the day of confirmation of PD by IIR and Cycle 1/Day 1 of the OOL Lenvatinib Treatment Period of less than or equal to 3 months.
4. No systemic anticancer treatment during the interval between the day of confirmation of PD by the IIR and Cycle 1/Day 1 of the OOL Lenvatinib Treatment Period.
Inclusion Criteria
Inclusion criteria:
1. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC).
2. Measurable disease according to (RECIST 1.1) and confirmed by central radiographic review.
3. 131 I-refractory/resistant disease.
4. Evidence of disease progression within 12 months prior to signing informed consent (+1 month screening window).
5. Prior treatment with 0 or 1 vascular endothelial growth-factor (VEGF) or vascular endothelial growth-factor receptors (VEGFR) targeted therapy.
6. Adequate renal, liver, bone marrow, and blood coagulation function, as defined in the protocol.
Inclusion criteria for OOL Lenvatinib Treatment Period :
Participants were eligible for lenvatinib treatment in the OOL Lenvatinib Treatment Period if the met the following criteria:
1. Placebo-treated participants in the Randomization Phase who had progressive disease (PD) confirmed by IIR, and who requested treatment with lenvatinib.
2. Participants who continued to satisfy specified inclusion and
1. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC).
2. Measurable disease according to (RECIST 1.1) and confirmed by central radiographic review.
3. 131 I-refractory/resistant disease.
4. Evidence of disease progression within 12 months prior to signing informed consent (+1 month screening window).
5. Prior treatment with 0 or 1 vascular endothelial growth-factor (VEGF) or vascular endothelial growth-factor receptors (VEGFR) targeted therapy.
6. Adequate renal, liver, bone marrow, and blood coagulation function, as defined in the protocol.
Inclusion criteria for OOL Lenvatinib Treatment Period :
Participants were eligible for lenvatinib treatment in the OOL Lenvatinib Treatment Period if the met the following criteria:
1. Placebo-treated participants in the Randomization Phase who had progressive disease (PD) confirmed by IIR, and who requested treatment with lenvatinib.
2. Participants who continued to satisfy specified inclusion and
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01321554
Org Class
Industry
Org Full Name
Eisai Inc.
Org Study Id
E7080-G000-303
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer
Primary Outcomes
Outcome Description
PFS was defined as the time from the date of randomization to the date of first documentation of disease progression or death (whichever occurred first), as determined by blinded IIR using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for the double-blind treatment period (Randomization Phase). 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.
Outcome Measure
Progression Free Survival (PFS)
Outcome Time Frame
Date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 years
Secondary Ids
Secondary Id
2010-023783-41
Secondary Outcomes
Outcome Description
ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by blinded IIR using RECIST 1.1 for target lesions and assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans (for double blind treatment period i.e. Randomization Phase). 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. ORR = CR + PR.
Outcome Time Frame
Date of randomization to the date of disease progression or death (whichever occurred first), assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 years
Outcome Measure
Overall Response Rate (ORR)
Outcome Description
Overall survival measured from the date of randomization until date of death from any cause. Overall survival is adjusted with rank preserving structural failure time.
Outcome Time Frame
Date of randomization until date of death from any cause, assessed up to data cutoff date (15 Nov 2013) or up to approximately 2.5 years
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose
Outcome Measure
Pharmacokinetic (PK) Profile of Lenvatinib: Area Under the Plasma Concentration Curve
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404