A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC) (SELECT)

Eisai

Status and phase: Completed; Phase 3

Conditions: Thyroid Cancer

Treatments: Drug: Lenvatinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01321554

E7080-G000-303

2010-023783-41 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 392 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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392 participants in 4 patient groups, including a placebo group

Lenvatinib (Randomization Phase)

Experimental group

Description:

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.

Treatment:

Drug: Lenvatinib

Drug: Lenvatinib

Placebo (Randomization Phase)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Lenvatinib 24 mg (OOL Lenvatinib Treatment Period)

Experimental group

Description:

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.

Treatment:

Drug: Lenvatinib

Drug: Lenvatinib

Lenvatinib 20 mg (OOL Lenvatinib Treatment Period)

Experimental group

Description:

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.

Treatment:

Drug: Lenvatinib

Drug: Lenvatinib