A Phase 2 trial studying how lenvatinib works in combination with Ifosfamide and Etoposide compared to Ifosfamide and Etoposide in treating Children, Adolescents and Young Adults for a type of cancer that is not responding to treatment or has reappeared following an initial recovery.
- Conditions
- Relapsed or Refractory OsteosarcomaMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003696-19-ES
- 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
- 81
1. Histologically or cytologically confirmed diagnosis of high grade osteosarcoma.
2. Refractory or relapsed osteosarcoma after 1 to 2 prior systemic treatments.
3. Measurable or evaluable disease per RECIST 1.1 that meets the following criteria:
- Must be accurately measurable with a minimum size (by long axis) of 10 mm using computed tomography/magnetic resonance imaging (CT/MRI) (lymph nodes must be accurately measurable with a minimum size [by short axis] of 15 mm).
- 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.
4. Aged 2 years to =25 years at the time of informed consent.
5. Life expectancy of 12 weeks or more.
6. Lansky play score =50% or Karnofsky Performance Status score = 50%. Use Karnofsky for subjects =16 years of age and Lansky for subjects <16 years of age. Subjects who are unable to walk because of paralysis, but who are up in wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
7. Adequate bone marrow function as evidenced by:
a. absolute neutrophil count (ANC) =1.0×10^9/L. (subjects with bone marrow involvement should have ANC =0.8×10^9/L and leucocyte count =1×10^9/L).
b. hemoglobin =8.0 g/dL (a hemoglobin of <8.0 g/dL is acceptable if it is corrected by growth factor or transfusion before Cycle 1 Day 1).
c. platelet count =75×109/L.
8. Adequate blood coagulation function defined by International Normalized ratio (INR) =1.5 unless participant is receiving anticoagulant therapy, as long as INR is within therapeutic range of intended use of anticoagulants.
9. Adequate liver function as evidenced by:
a. bilirubin =1.5 times the upper limit of normal (ULN).
b. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =3×ULN (in the case of liver metastases =5×ULN).
10. Adequate renal function as evidenced by:
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 within the protocol page 5, then creatinine clearance (or radioisotope glomerular filtration rate [GFR]) must be >70 mL/min/1.73 m2.
b. Urine dipstick <2+ for proteinuria. Subjects who have =2+ proteinuria on dipstick urinalysis should undergo a spot protein-creatinine (P/C) ratio test that should be Grade <2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and if possible perform a 24-hour urine collection (children and adolescents =12 years of age must have =500 mg of protein/24 hours and subjects >12 years of age must have =1 g of protein/24 hours).
c. No clinical evidence of nephrotic syndrome.
11. Adequate cardiac function as evidenced by left ventricular ejection fraction =50% at baseline as determined by echocardiography.
12. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as:
a. BP <95th percentile for sex, age, and height/length at screening (as per National Heart Lung and Blood Institute guidelines) and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.
Subjects >18 years of age should have BP =150/90 mm Hg at screening and no change in antihypertensive therapy within 1 week prior to Cycle 1 Day 1.
13. Washout before Cycle 1 Day 1 of 3 weeks in case of prior chemotherapy, 6 weeks if treatment included nitrosoureas; 4 weeks for definitive radiotherapy, 2 weeks for palliative rad
1. Any active infection or infectious illness unless fully recovered prior to Cycle 1 Day 1.
2. Subjects with central nervous system metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication at least 2 weeks before C1D1
3. Active second malignancy within 2 years prior to enrollment
4. Any medical or other condition that in the opinion of the investigator(s) would preclude the subject's participation in a clinical study.
5. Has had major surgery within 3 weeks prior to Cycle 1 Day 1.
6. Known hypersensitivity to any component(s) of the study drugs (lenvatinib, ifosfamide, and etoposide, or their ingredients).
7. Currently receiving any investigational drug or device in another clinical study or within 28 days prior to Cycle 1 Day 1.
8. A clinically significant ECG abnormality, including a marked baseline prolonged QT or QTc interval (eg, a repeated demonstration of a QTc interval >480 msec).
9. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib.
10. Pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula.
11. Gastrointestinal bleeding or active hemoptysis (bright red blood of at least ½ teaspoon) within 3 weeks prior to Cycle 1 Day 1.
12. Radiographic evidence of intratumoral cavitation, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy.
13. History of ifosfamide-related Grade =3 nephrotoxicity or encephalopathy.
14. Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments.
15. Known to be human immunodeficiency virus (HIV) positive. Note: HIV testing is required at screening only when mandated by local authority.
16. Active viral hepatitis (B or C) as demonstrated by positive serology. Note: Testing for Hepatitis B or Hepatitis C is required at screening only when mandated by local health authority.
17. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ßhCG]) (human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG /hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of any study drug.
18. Females of childbearing potential* who:
- Do not agree to use a highly effective method of contraception for the entire study period and for 28 days after lenvatinib discontinuation or 12 months after etoposide and ifosfamide discontinuation, ie:
? total abstinence (if it is their preferred and usual lifestyle)
? an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
? A contraceptive implant
? an oral contraceptive. Subject must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing with study drug and throughout the study and for 28 days after lenvatinib discontinuation or 12 months after etoposide and ifosfamide discontinuation .
OR
- Do not have a vasectomized partner with confirmed azoosper
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