Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumors, Including Central Nervous System Tumors

* Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur

* Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ≥21 days after the completion of interleukins, interferons or cytokines (other than hematopoietic growth factors)

* Stem cell infusions (with or without total body irradiation): Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor leukocytes infusion or boost infusion: ≥84 days after infusion and no evidence of graft versus host disease; Autologous stem cell infusion including boost infusion: ≥42 days

* Cellular Therapy: ≥42 days after the completion of any type of cellular therapy (eg, modified T cells, natural killer cells, dendritic cells, etc)

* Radiotherapy (XRT)/External Beam Irradiation including Protons: ≥14 days after local XRT; ≥150 days after total body irradiation, craniospinal XRT or if radiation to ≥50% of the pelvis; ≥42 days if other substantial bone marrow radiation.

* Radiopharmaceutical therapy: ≥42 days after systemically administered therapy.

* Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted or mammalian target of rapamycin (mTOR)-targeted therapies: Must not have received prior exposure to lenvatinib; May have previously progressed on an mTOR inhibitor; No more than 2 prior VEGF/VEGFR-targeted therapies (For Phase 2 only); Must not have received prior VEGF/VEGFR-targeted therapy in combination with an mTOR inhibitor (For Phase 2 only)

Adequate bone marrow function for participants with solid tumors without known bone marrow involvement

Adequate bone marrow function for participants with known bone marrow metastatic disease

Adequate renal function

Adequate liver function

Adequate cardiac function

Adequate neurologic function

Adequate blood pressure (BP) control with or without antihypertensive medications

Adequate coagulation

Adequate pancreatic function

Adequate metabolic function

Adequate glycemic control

Participants must have a minimum body surface area (BSA) of 0.6 m\^2 at study entry.

Participants who have had or are planning to have the following invasive procedures

* Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrolment

* Central line placement or subcutaneous port placement is not considered major surgery. External central lines must be placed at least 3 days prior to enrollment and subcutaneous ports must be placed at least 7 days prior to enrollment

* Fine needle aspirate within 7 days prior to enrolment

* Surgical or other wounds must be adequately healed prior to enrolment

* For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy

Participants who have non-healing wound, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrolment

Participants having an active infection requiring systemic therapy.

Participants with a known history of active hepatitis B (defined as hepatitis B surface antigen reactive or hepatitis B virus- deoxyribonucleic \[DNA\] detected) or known active hepatitis C virus (HCV, defined as HCV- Ribonucleic acid \[RNA\] detected). Note: No testing for hepatitis B and hepatitis C is required unless mandated by the local health authority.

Known to be human immunodeficiency virus (HIV) positive. Note: HIV testing is required at screening only when mandated by the local health authority

Clinical evidence of nephrotic syndrome prior to enrolment

Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 21 days prior to enrolment

Thrombotic/ thromboembolic event requiring systemic anticoagulation within 90 days prior to enrollment

Evidence of new intracranial hemorrhage of more than punctate size on MRI assessment obtained within 28 days prior to study enrollment for Participants with HGG

Diagnosis of lymphoma

Radiographic evidence of major blood vessel invasion/infiltration.

Evidence of untreated CNS metastases (exception: participants with primary CNS tumors and leptomeningeal disease)

Participants who are currently receiving enzyme-inducing anticonvulsants

Participants chronically receiving strong cytochrome P450 3A4 (CYP3A4)/P-glycoprotein (P-gp) inhibitors or inducers within 7 days prior to study enrollment

Females who are breastfeeding or pregnant. For females of childbearing potential, a negative screening pregnancy test must be obtained within 72 hours before the first dose of study drug

Males who have not had a successful vasectomy (confirmed azoospermia) or if they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 7 days after lenvatinib discontinuation or 4 weeks after discontinuation of everolimus). No sperm donation is allowed during the study period and for 7 days after lenvatinib discontinuation or 4 weeks after discontinuation of everolimus.

What this study is about