A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer
Overview
- Phase
- Phase 3
- Intervention
- Lenvatinib
- Conditions
- Thyroid Cancer
- Sponsor
- Eisai Inc.
- Enrollment
- 392
- Locations
- 7
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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).
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Lenvatinib (Randomization Phase)
Participants randomly assigned in a 2:1 ratio to receive blinded study drug (lenvatinib or matching placebo) until documentation of disease progression (confirmed by IIR), development of unacceptable toxicity, or withdrawal of consent.
Intervention: Lenvatinib
Placebo (Randomization Phase)
Participants randomly assigned in a 2:1 ratio to receive blinded study drug (lenvatinib or matching placebo) until documentation of disease progression (confirmed by IIR), development of unacceptable toxicity, or withdrawal of consent.
Intervention: Placebo
Lenvatinib 24 mg (OOL Lenvatinib Treatment Period)
Participants will receive lenvatinib 24 mg, orally once daily until documentation of disease progression (confirmed by investigator's assessment), development of unacceptable toxicity, or withdrawal of consent. Placebo treated participants in the Randomization Phase who have progressive disease confirmed by IIR could request to receive lenvatinib treatment in the OOL Treatment Period.
Intervention: Lenvatinib
Lenvatinib 20 mg (OOL Lenvatinib Treatment Period)
Participants will receive lenvatinib 20 mg, orally once daily until documentation of disease progression (confirmed by investigator's assessment), development of unacceptable toxicity, or withdrawal of consent. Placebo treated participants in the Randomization Phase who have progressive disease confirmed by IIR could request to receive lenvatinib treatment in the OOL Treatment Period.
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
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
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.
Secondary Outcomes
- Overall Survival (OS)(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)
- Overall Response Rate (ORR)(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)
- Pharmacokinetic (PK) Profile of Lenvatinib: Area Under the Plasma Concentration Curve(Cycle 1 Days 1 and 15: 0-10 hours postdose; Cycle 2 Day 1: 0-12 hour postdose)