Study of Lenvatinib in Children and Adolescents With Refractory or Relapsed Solid Malignancies and Young Adults With Osteosarcoma

Completed · Phase 1/Phase 2

Conditions studied: Tumors, Solid Malignant Tumors, Osteosarcoma, Differentiated Thyroid Cancer (DTC)

In brief

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).

Key facts

Study ID

NCT02432274

Run by

Eisai Limited

People needed

117

Starts

2014-12-29

Expected to finish

2022-07-20

Last updated by the study team

2023-07-11

Who can join

Age: 2 and older, up to 25. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically or cytologically confirmed diagnosis of solid malignant tumor.
• Cohort 1: Any solid malignant tumor.
• Cohort 2A: Differentiated Thyroid Cancer (DTC) with one of the following histological subtypes:
• i) Papillary thyroid cancer (PTC). i.a) Follicular variant. i.b) Other variants (including but not limited to tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hurthle cell variant of papillary carcinoma, or poorly differentiated carcinomas).
• ii) Follicular thyroid cancer (FTC). ii.a) Hurthle cell. ii.b) Clear cell. ii.c) Insular.
• c) Cohort 2B, 3A, and 3B: Relapsed or refractory osteosarcoma.
• Relapsed or refractory solid tumor malignancy that has progressed on standard anticancer therapy with no available curative options. (Note: Osteosarcoma participants must be in first or subsequent relapse [greater than or equal to first relapse]). Only the osteosarcoma participants enrolled to Cohorts 3A and 3B must be deemed candidates for ifosfamide and etoposide chemotherapy).
• Evaluable or measurable disease that meets the following criteria:
• Participants must have evaluable or measurable disease based on RECIST 1.1 using computed tomography (CT)/magnetic resonance imaging (MRI).
• Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have subsequently grown unequivocally to be deemed a target lesion.
• DTC participants must be 131 iodine-refractory/ relapsed as defined by at least one of the following:
• One or more evaluable or measurable lesions that do not demonstrate iodine uptake on any radioiodine scan; or
• One or more evaluable or measurable lesions that have progressed based on RECIST 1.1, within 12 months of 131 iodine therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning. These participants must not be eligible for possible curative surgery; or
• Cumulative activity of 131 iodine greater than 400 millicuries (mCi) or 14.8 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry.
• Participants with DTC must be receiving thyroxine suppression therapy and levels of thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than or equal to 5.50 milliunits per liter (mU/L)). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH less than 0.50 mU/L).
• Participants with known central nervous system (CNS) primary tumors or metastases who have completed brain therapy (such as radiotherapy, stereotactic radiosurgery, or surgical resection) and have remained clinically stable, asymptomatic, and off of steroids for 2 weeks prior to Cycle 1 Day 1 will be eligible.
• Male or female participants age 2 years to less than18 years and less than or equal to 25 years for osteosarcoma subjects at the time of informed consent.
• Lansky play score greater than or equal to 50% or Karnofsky Performance Status score greater than or equal to 50%. Use Karnofsky for participants greater than or equal to 16 years of age and Lansky for participants less than 16 years of age.
• Life expectancy greater than or equal to 3 months.
• Adequate bone marrow function as evidenced by:
• absolute neutrophil count (ANC) greater than or equal to 1.0 x 10\^9/L (for Cohorts 3A and 3B leucocyte count greater than or equal to 2 x 10\^9/L; participants with bone marrow involvement should have ANC greater than or equal to 0.8 x 10\^9/L and leucocyte count greater than or equal to 1 x 10\^9/L).
• hemoglobin greater than or equal to 8.0 grams/deciliter (g/dL) (a hemoglobin less than 8.0 g/dL is acceptable if it is corrected by growth factor or transfusion before starting lenvatinib).
• platelet count greater than or equal to 75 x 10\^9/L.
• Adequate liver function as evidenced by:
• bilirubin less than or equal 1.5 times the upper limit of normal (ULN).

You may not qualify if…

• Any active infection or infectious illness unless fully recovered prior to dosing.
• Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
• Other organ toxicity due to prior anticancer therapy (investigational agent, chemotherapy, or radiation therapy) except alopecia, and ototoxicity due to cisplatin not already covered in the inclusion/exclusion criteria, which has not recovered to Grade less than 2 per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
• Known hypersensitivity to any component of the product (lenvatinib or ingredients).
• Concurrent administration of any other antitumor therapy.
• Previous treatment with lenvatinib (except for participants previously enrolled into Cohorts 1 or 2B of this study).
• Two or more prior vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) targeted therapies.
• Currently receiving any investigational drug or device in another clinical trial or within 30 days preceding informed consent.
• A clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval greater than 480 msec).
• Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib.
• Gastrointestinal bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 3 weeks prior to the first dose of study drug.
• Active second malignancy within 2 years prior to enrollment ([in addition to the primary tumor types specified by cohort in Inclusion Criterion Number 1], but not including definitively treated superficial melanoma, in-situ, basal or squamous cell carcinoma of the skin).
• Previous treatment with ifosfamide and Grade greater than or equal to 3 nephrotoxicity or encephalopathy (Cohorts 3A and 3B).
• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
• Cohort 3B (Combination Expansion): Osteosarcoma participants who progressed in Cohorts 1 or 2B and opt to receive combination therapy.
• Osteosarcoma participants receiving combination therapy of lenvatinib with ifosfamide and etoposide should meet all the exclusion criteria, with the exception of Criterion Number 6.

Where it is running

• Texas Children's Hospital — Houston, Texas, United States
• CHU Strasbourg - Hopital Hautepierre — Strasbourg, Bas Rhin, France
• Centre Oscar Lambret Lille — Lille, Rhone, France
• Centre Leon Berard — Lyon, Rhone, France
• CHU Nantes - Hopital Mere-Enfant — Nantes, France
• Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris — Paris, France
• Institut Gustave Roussy — Paris, France
• CHU de Toulouse - Hopital des Enfants — Toulouse, France
• Universitaetsklinikum Muenster — Münster, Germany
• Kinderklinik des Olga hospitals — Stuttgart, Germany
• Istituto Ortopedico Rizzoli — Bologna, Italy
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan, Italy
• Ospedale Pediatrico Bambino Gesu — Roma, Italy
• Hospital Universitari Vall d'Hebron — Barcelona, Spain
• Hospital Infantil Universitario Nino Jesus — Madrid, Spain
• Hospital Universitario y Politecnico La Fe Hospital La Fe Valencia — Valencia, Spain
• Birmingham Children's Hospital — Birmingham, United Kingdom
• University College London Hospital — London, United Kingdom
• Royal Victoria Infirmary — Newcastle, United Kingdom

Full record on ClinicalTrials.gov

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