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

Phase 1

• Conditions: Refractory or relapsed solid malignancies; MedDRA version: 19.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-005534-38-Outside-EU/EEA
• Lead Sponsor: Eisai Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-23
• Last Update Posted: 28 November 2016

Recruitment & Eligibility

• Status: A
• 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 of the following histological subtypes:
i.Papillary thyroid cancer (PTC)
1.Follicular variant
2.Other variants (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 (FTC)
1.Hürthle cell
2.Clear cell
3.Insular
c. Cohort 2B, 3A and 3B:Relapsed or refractory osteosarcoma
2.Relapsed or refractory solid tumor malignancy that has progressed on standard anticancer therapy with no available curative options.
3.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 RECIST 1.1
b.Subjects with DTC in Cohort 2A:
i.Must have measurable 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.
ii.Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies must have subsequently grown unequivocally to be deemed a target lesion
4.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
5.Subjects with DTC must be receiving thyroxine suppression therapy and levels of thyroid stimulating hormone should be =5.50 mU/L).
6.Subjects with known CNS primary tumors or metastases who have completed brain therapy (such as radiotherapy), stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic and off of steroids for 4 weeks prior to Cycle 1 Day 1.
7.Male or female subjects age 2 years to <18 years
8.Lansky play score =70% or Karnofsky Performance Status score =70%
9.Life expectancy =3 months
10.Adequate bone marrow function
11.Adequate liver function:
a.bilirubin =1.5 times the upper limit of normal (ULN)
b.alkaline phosphatase, ALT, and AST = 3 × ULN (in the case of liver metastases =5 × ULN)
12.Adequate renal function:
a.Serum creatinine =1.5 × ULN for age/gender
b.Urine dipstick <2+ for proteinuria.
c.No clinical evidence of nephrotic syndrome
13.Adequate cardiac function as evidenced by Fractional Shortening =28% (=35% for children <3 yrs of age) or left ventricular ejection fraction =50%)
14.Adequately controlled blood pressure (BP)
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
15.Washout of 3 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas; 4 weeks for definitive radiotherapy and 2 weeks for palliative radiotherapy, 3 months from high-dose chemotherapy and stem cell rescue
16.Females must not be lactating or pregnant at Screening or Baseline
17.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

Exclusion Criteria

1. Any active 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, and ototoxicty due top cisplatin 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 1 or 2 of this study)
7. Two or more prior VEGF/VEGFR-targeted therapies
8. Currentlyreceiving any investigational drug or device in another clinical trial 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 superficial melanoma, carcinoma in-situ, basal or squamous cell
carcinoma of the skin)
13. Osteosarcoma subjects receiving combination therapy of lenvatinib with ifosfamide and etoposide should meet all the exclusion criteria, with the exception of Criterion Number 6.
14.Previous treatment with ifosfamide and grade =3 nephrotoxicity or encephalopathy (Cohorts 3A and 3B)

Study & Design

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