A Phase 1b/2 trial studying how well lenvatinib works in treating children, adolescents and young adults with different types of cancer that are not responding to treatment or have reappeared following an initial recovery
- Conditions
- Refractory or relapsed solid malignanciesMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-005534-38-GB
- Lead Sponsor
- Eisai Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 108
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.Evaluable or measurable disease that meets the following criteria
a. Subjects must have evaluable or measurable disease based on RECIST 1.1
b.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 at least one of the following:
a.One or more evaluable or measurable lesions that do not demonstrate iodine uptake on any radioiodine scan OR
b.One or more evaluable or measurable lesions that have progressed based on RECIST 1.1, within 12 months of 131I therapy, despite demonstration of radioiodine avidity at the time of that treatment by pre- or post-treatment scanning. These subjects must not be eligible for possible curative surgery OR
c.Cumulative activity of 131I >400 millicuries (mCi) or 14.8 gigabecquerels (GBq), 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 (TSH) should not be elevated (TSH should be =5.50 mU/L). When tolerated by the subject, thyroxine dose should be changed to achieve TSH suppression (TSH <0.50 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, (=25 years for osteosarcoma subjects) at the time of informed consent
8.Lansky play score =50% or Karnofsky Performance Status score =50%
9.Life expectancy = 3 monthss
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 based on age/gender as below. If serum creatinine is greater than maximum serum creatinine for age/gender as shown in the table below, then creatinine clearance (or radioisotope glomerular filtration rate [GFR]) must be >70 mL/min/1.73 m2 (Appendix 6).
Age Max. Serum Creatinine (mg/dL)
Male Female
2 to < 6 years 0.8 0.8
6 to < 10 years 1 1
10 to < 13 years 1.2 1.2
13 to < 16 years 1.5 1.4
= 16 years 1.7 1.4
b.Urine dipstick <2+ for proteinuria.
c.No clinical evidence of nephrotic syndrome
13. Adequate cardiac function as evidenced by Fractional
Subjects who meet any of the following criteria will be excluded from this study:
1.Any active infection or infectious illness unless fully recovered prior to dosing
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 ototoxicity due to cisplatin not already covered in the inclusion/exclusion criteria, which has not recovered to Grade <2 per CTCAE v4.03
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 Cohorts 1 or 2B of this study)
7.Two or more prior VEGF/VEGFR-targeted therapies
8.Currently receiving any investigational drug or device in another clinical trial or 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, in-situ, basal or squamous cell carcinoma of the skin).
13.Previous treatment with ifosfamide and grade =3 nephrotoxicity or encephalopathy (Cohorts 3A and 3B).
14.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.
Females of childbearing potential who:
•Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
ototal abstinence (if it is their preferred and usual lifestyle)
o an intrauterine device or intrauterine hormone-releasing system (IUS)
o an oral contraceptive. Subject must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 6 months after study drug discontinuation.) .
o have a vasectomized partner with confirmed azoospermia.
•Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 6 months after study drug discontinuation.
Cohort 3B (Combination Expansion): Osteosarcoma subjects who progressed in Cohorts 1 or 2B and opt to receive combination therapy:
15.Osteosarcoma subjects receiving combination therapy of lenvatinib with etoposide and ifosfamide 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
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method