A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)
Condition: Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: Lenvatinib; Placebo; Lenvatinib
Intervention description: Lenvatinib 24 mg (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously. Dose interruptions or reductions were allowed for subjects who experienced treatment-related toxicity.; Matching placebo (two 10-mg and one 4-mg lenvatinib matched capsules) taken orally once daily, continuously.; Lenvatinib 20 mg (two 10-mg capsules) taken orally once daily, continuously. Dose interruptions or reductions were allowed for subjects who experienced treatment-related toxicity.
The dose of lenvatinib during the OOL Lenvatinib Treatment Period was 24 mg once daily from 03 Oct 2011 until 15 Feb 2013. The dose was lowered at the request of the Data Monitoring Committee to 20 mg on 16 Feb 2013. Thus, more subjects were treated with 24 mg starting dose and the treatment duration was longer for these participants than those whose starting dose was 20 mg.
Intervention MeSH terms: Lenvatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 392.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).
    

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.