A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors

Protocol: 
AAAR4705
Phase: 
I/II

A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including CNS Tumors

This is a Phase 1/2 multicenter study of lenvatinib administered in
combination with everolimus in pediatric patients with solid tumors which
have come back or have not responded to the standard therapy, including
Ewing sarcoma/peripheral primitive neuroectodermal tumor (pPNET),
rhabdomyosarcoma, and high grade glioma (HGG). The study treatment is
considered experimental because lenvatinib is not approved by the United
States (US) Food and Drug Administration (FDA) for treating pediatric
patients with refractory solid tumors. The purpose of this study is to
determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
(RP2D) of lenvatinib administered in combination with everolimus. Another
objective is to define the toxicities of lenvatinib administered in
combination with everolimus in pediatric patients with recurrent/refractory
solid tumors.

Lenvatinib and everolimus will be administered every day orally for 28-day
treatment cycles. Blood samples will be collected to determine how much
lenvatinib and everolimus is in the blood during the study
(pharmacokinetics). Blood and tissue samples will also be collected to
determine how genes affect the ability to absorb, distribute, breakdown and
excrete lenvatinib and everolimus. Disease assessment will be performed at
baseline, at the end of cycle 1 (week 4), at week 12, week 24, and then
every 12 weeks, or as clinically indicated.

The phase 1 component of the study is a dose escalation study with the
initial dose level (Dose Level 1) for lenvatinib at 11 mg/m2. The initial
dose of everolimus is 3 mg/m2. Once the MTD/RP2D of the combination of
lenvatinib and everolimus in pediatric population has been determined in
Phase 1, the Phase 2 portion of this pediatric study will open to accrual
with Cohort 1 (recurrent or refractory Ewing sarcoma/pPNET), Cohort 2
(recurrent or refractory rhabdomyosarcoma), and Cohort 3 (recurrent or
refractory HGG).

Are you Eligible? (Inclusion Criteria)

Patients must be ≥2 years and ≤21 years of age at the time of enrollment.

Phase 1: Patients must have histologically or cytologically confirmed
diagnosis of recurrent or refractory solid tumors (excluding hepatoblastoma
and lymphomas), including primary central nervous system (CNS) tumors.

Phase 2: Patients must have measurable tumors which have come back or have
not responded to the standard therapy.
Cohort 1: Ewing sarcoma/pPNET
Cohort 2: Rhabdomyosarcoma
Cohort 3: HGG

Patients must have fully recovered from the side effects of all prior anti-
cancer therapies including chemotherapy, immunotherapy, or radiotherapy.

Trial Location

Herbert Irving Comprehensive Cancer Center
161 Fort Washington Ave.
Herbert Irving Pavilion
New York, NY 10032
United States