Study of Lenvatinib in Children and Adolescents With Refractory or Relapsed Solid Malignancies and Young Adults With Osteosarcoma
Condition: Tumors; Solid Malignant Tumors; Osteosarcoma; Differentiated Thyroid Cancer (DTC)
MeSH terms: Neoplasms; Thyroid Neoplasms; Osteosarcoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a phase 1/2 study evaluating safety, tolerability, and efficacy of lenvatinib as
      single-agent, and in combination with chemotherapy (ifosfamide and etoposide) in children and
      adolescents with refractory or relapsed solid malignancies including differentiated thyroid
      carcinoma (single agent lenvatinib) and osteosarcoma (single agent and combination
      lenvatinib).
    

Detailed description: 
      The study consists of 5 cohorts:

      Cohort 1 (Single-Agent Dose-Finding) dose-escalation to find the recommended dose (RD) of
      lenvatinib using time-to-event continual reassessment method (TiTE-CRM) in children and
      adolescents with relapsed or refractory solid malignant tumors. When the RD is identified,
      Cohorts 2A, 2B, and 3A will enroll in parallel.

      Cohort 2 (Single-Agent Expansion) will evaluate the efficacy of lenvatinib at the RD in
      children, adolescents, and young adults with

        1. 131 iodine-refractory differentiated thyroid cancer (DTC) [Cohort 2A] or

        2. Relapsed or refractory osteosarcoma [Cohort 2B]

      Cohort 3A (Combination Dose-Finding) will determine the RD of lenvatinib in combination with
      ifosfamide and etoposide in children, adolescents, and young adults with relapsed or
      refractory osteosarcoma.

      Cohort 3B (Combination Expansion) will evaluate the efficacy of lenvatinib at the RD from
      Cohort 3A in combination with ifosfamide and etoposide in children, adolescents, and young
      adults with relapsed or refractory osteosarcoma. Participants with osteosarcoma who have
      enrolled into Cohort 1 or 2B and experienced progressive disease will also be candidates for
      enrollment in Cohort 3B.

      Lenvatinib will be provided as hard capsules containing 1, 4, or 10 mg lenvatinib. Lenvatinib
      capsules should be dissolved in water or apple juice for those who are unable to swallow
      capsules.
    

Intervention name(s): Lenvatinib; Lenvatinib; Lenvatinib; Lenvatinib; Lenvatinib; Ifosfamide; Etoposide; Ifosfamide; Etoposide
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Cohort 1: Lenvatinib will be administered orally, once daily on Days 1 to 28 of each 28-day cycle at a starting dose of 11 mg/m2. Dose can be de-escalated to 9 mg/m2 or escalated to 14 and 17 mg/m2.; Cohort 2A: Lenvatinib (RD determined in Cohort 1) will be administered orally, once daily on Days 1 to 28 of each 28-day cycle.; Cohort 2B: Lenvatinib (RD determined in Cohort 1) will be administered orally, once daily on Days 1 to 28 of each 28-day cycle.; Cohort 3A: Lenvatinib will be administered orally, once daily on Days 1 to 21 of each 21-day cycle at 20% lower than RD determined in Cohort 1 (starting dose). Lenvatinib dose can be escalated to the RD from Cohort 1 or de-escalated to 40 and 60% lower than the RD from Cohort 1.; Cohort 3B: Lenvatinib will be administered orally, once daily on Days 1 to 21 of each 21-day cycle at the RD as determined in Cohort 3A.; Ifosfamide 3000 mg/m2/day (starting dose) will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. Ifosfamide dose can be de-escalated to 2400 mg/m2/day and 1800 mg/m2/day.; Etoposide 100 mg/m2/day (starting dose) will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles. Etoposide dose can be de-escalated to 80 mg/m2/day and 60 mg/m2/day.; Ifosfamide dose identified in Cohort 3A will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.; Etoposide dose identified in Cohort 3A will be administered on Days 1 to 3 of each 21-day cycle for a total of 5 cycles.
Other intervention name(s): E7080, lenvatinib; E7080, lenvatinib; E7080, lenvatinib; E7080, lenvatinib; E7080, lenvatinib
Intervention MeSH terms: Etoposide; Etoposide phosphate; Lenvatinib; Ifosfamide; Isophosphamide mustard
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: E7080; Lenvatinib; Solid malignancies; Osteosarcoma; Differentiated Thyroid Cancer