A Phase 1b/2 trial studying how well lenvatinib works in treating children and adolescents with different types of cancer that are not responding to treatment or have reappeared following an initial recovery

• Conditions: Refractory or relapsed solid malignancies; MedDRA version: 17.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-005534-38-ES
• Lead Sponsor: Eisai Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-27
• Last Update Posted: 6 January 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

1.Histologically or cytologically confirmed diagnosis of solid malignant
tumor a.Cohort 1: Any solid malignant tumor b.Cohort 2A: DTC with one histological subtype:i.Papillary thyroid cancer
1.Follicular variant 2.Other (tall cell, columnar cell, cribriform-morular,solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis,Hürthle cell variant of papillary or poorly differentiated carcinomas)ii.Follicular thyroid cancer 1.Hürthle cell 2.Clear cell 3.Insular2.Relapsed or refractory solid tumor malignancy that has progressed onstandard anticancer therapy with no available curative options3.Evidence of metastases4.Measurable disease that meets the following criteria a.Subjects with osteosarcoma and other tumor types who are in the dose-finding cohorts(Cohort 1 and Cohort 3A) must have evaluable disease based on RECIST1.1 b.Subjects with DTC in Cohort 2A: i.Must have disease meeting the
following criteria: At least 1 lesion of ?1.0 cm in the longest diameter for a non-lymph node or ?1.5 cm in the short-axis diameter for a lymph node. For Cohort 2, if there is only 1 target lesion and it is a non-lymph node, it should have a longest diameter of ?1.5 cm ii.Lesions that have had external beam radiotherapy or locoregional therapies must have subsequently grown unequivocally to be deemed a target lesion 5.DTC subjects must be 131I-refractory/ relapsed as defined by a.One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan OR b.have progressed based on RECIST 1.1 within 12 months of 131I therapy OR c.Cumulative activity of 131I >600 millicuries or 22 gigabecquerels with the last dose administered at least 6 months prior to study entry 6.Subjects with DTC must be receiving thyroxine suppression therapy and levels of thyroid stimulating hormone should be ?5.50 mU/L).7.Subjects with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical
resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for 1 month prior to study entry 8.Male or female subjects age 12 years to <18 years 9.Lansky play score ?70% or ECOG ?1 10.Life expectancy ?3 months
11.Adequate bone marrow function
12.Adequate liver function:
a.bilirubin ?1.5 times the upper limit of normal (ULN)
b.alkaline phosphatase, alanine aminotransferase, and aspartate
aminotransferase ? 3 × ULN (in the case of liver metastases ?5 × ULN)
13.Adequate renal function:
a.Serum creatinine ?1.5 × ULN for age.
b.Urine dipstick <2+ for proteinuria.
c.No clinical evidence of nephrotic syndrome
14.Adequate cardiac function as evidenced by Fractional Shortening ?
28% and left ventricular ejection fraction ?50%)
15.Adequately controlled blood pressure
a.BP <95th percentile for sex, age, and height/length at screening and
no change in antihypertensive medications within 1-week prior to Cycle
1/Day 1
16.Washout of 3 weeks in case of prior chemotherapy, 6 weeks if
treatment included nitrosoureas; 4 weeks in case of prior radiotherapy, 3
months from high-dose chemotherapy and stem cell rescue
17.Females must not be lactating or pregnant at Screening or Baseline
18.All post pubertal females will be considered to be of childbearing
potential unless they have early menopause due to prior treatment
procedures or have been sterilized surgically
19.Females of childbearing potential must not have had unprotected
sexual intercourse within 30 days before study entry and mu

Exclusion Criteria

1. Any history or evidence of severe acute or chronic infection or infectious illness unless fully recovered for at least 4 weeks prior to screening
2. Any medical or other condition that in the opinion of the investigator(s) would preclude the subject?s participation in a clinical study
3. Other organ toxicity due to prior anticancer therapy (investigational agent, chemotherapy, or radiation therapy) except alopecia, not already covered in the inclusion/exclusion criteria, which has not recovered to Grade <2 per CTCAE v4.0
4. Known hypersensitivity to any component of the product (lenvatinib or ingredients)
5. Concurrent administration of any other antitumor therapy
6. Previous treatment with lenvatinib (except for subjects previously enrolled into Cohort 3B of this study)
7. Two or more prior VEGF/VEGFR-targeted therapies
8. Currently enrolled in another clinical trial or used any investigational drug or device within 30 days preceding informed consent
9. A clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval >480 msec)
10. Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib
11. Gastrointestinal bleeding or active hemoptysis (bright red blood of at least ½ teaspoon) within 3 weeks prior to the first dose of study drug
12. 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 melanoma, carcinoma in-situ, basal or squamous cell
carcinoma of the skin)
13. Osteosarcoma subjects receiving combination therapy of lenvatinib with CPM and etoposide should meet all the exclusion criteria, with the exception of Criterion Number 6.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified