Status and phase
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About
Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of lenvatinib administered in combination with everolimus once daily to pediatric participants with recurrent/refractory solid tumors. Phase 2, utilizing Simon's optimal 2-stage design, will be conducted to estimate the antitumor activity of lenvatinib in combination with everolimus in pediatric participants with selected recurrent/refractory solid tumors including Ewing sarcoma, rhabdomyosarcoma, and high grade glioma (HGG) using objective response rate (ORR) at Week 16 as the outcome measure.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria
≥2 years and <18 years of age for enrolment in Phase 1 or ≥2 years and ≤21 years of age for enrolment in Phase 2.
Recurrent or refractory solid tumors
Histologically or cytologically confirmed diagnosis
Measurable disease that meets the following criteria (Phase 2):
Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
Karnofsky performance score ≥50 for participants>16 year of age and Lansky play score ≥50 for participants ≤16 years of age. Neurologic deficits in participants with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Prior Therapy
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.
Exclusion Criteria
Participants who have had or are planning to have the following invasive procedures
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.
Primary purpose
Allocation
Interventional model
Masking
64 participants in 4 patient groups
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Data sourced from clinicaltrials.gov
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