A Phase 1b/2 trial studying how well lenvatinib works in treating children and 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-DE
- Lead Sponsor
- Eisai Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 97
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 months
10.Adequate bone marrow function
11.Adequate liver function:
a.bilirubin :Sl.S times the upper limit of normal (ULN)
b.alkaline phosphatase, ALT, and AST = 3 x ULN (in the case of liver
metastases =5 x 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/l.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 Shortening =
28% (=35% for children <3 yrs of age)
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
3.0ther 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 [ßhCG]
(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