Refractory or relapsed solid malignancies MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Sponsors
Eisai Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
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.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 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
Exclusion criteria
Exclusion criteria: 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort 1 (Single-Agent Dose-Finding) ? Identify the recommended dose (RD) of lenvatinib as a single agent in children and adolescents with relapsed or refractory solid malignant tumors Cohort 2 (Single-Agent Expansion) ? Evaluate the activity of lenvatinib in 2 separate malignancy groups: o Cohort 2A: 131I- refractory differentiated thyroid cancer: by objective response rate (ORR) for subjects with measurable disease and by best overall response (BOR) for all subjects o Cohort 2B: Relapsed or refractory osteosarcoma: by progression-free survival at 4 months (PFS)-4 Cohort 3 (Combination Dose-Finding and Expansion) ? Cohort 3A (Combination Dose-Finding) To identify the RD of lenvatinib in combination with ifosfamide and etoposide in osteosarcoma subjects ? Cohort 3B (Combination Expansion) o Evaluate the activity of lenvatinib in combination with ifosfamide and etoposide in osteosarcoma subjects by PFS-4;Secondary Objective: Cohort 1 • Evaluate the activity of E7080 as assessed by BOR, ORR, DOR, PFS, time to progression (TTP), based on RECIST 1.1 • Assess the safety & toxicity profile of E7080 in children and adolescents and young adults Cohort 2 • Assess the safety and toxicity of E7080 as for Cohort 1 • Evaluate the efficacy of E7080 as assessed by BOR, ORR (osteosarcoma only), DOR, TTP, PFS , DCR and CBR Cohort 3 • Assess the safety & toxicity of E7080 in combination with IFO and etoposide in children, adolescents and young adults with relapsed or refractory osteosarcoma • Evaluate the efficacy of E7080 as assessed by BOR, ORR, DOR, TTP, PFS , DCR and CBR Cohorts 1,2&3 • Examine blood and tumor biomarkers and correlate with clinical response to E7080 • Assess bone growth and height during and after discontinuation of treatment with E7080 • Determine population-based PK parameters of E7080 Assess the palatability and acceptability of the suspension formulation of E7080;Primary end point(s): Cohort 1 (Single-Agent Dose-Finding) ? RD based on the TiT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Cohort 1 (Single-Agent Dose-Finding): Efficacy o BOR over the treatment period o ORR o DOR o PFS o Disease Control Rate (DCR) defined as the percentage of subjects who have a BOR of CR or PR or stable disease (SD). To be assigned a best overall response of SD, the time from the first administration of study drug until the date of documented SD should be =7 weeks. o Durable SD rate defined as the percentage of subjects who have the duration of SD lasting = 23 weeks o Clinical Benefit Rate (CBR) defined as the percentage of subjects who have a BOR of CR or PR or durable SD o TTP defined as the time from the date of the first administration of study drug until the date of first documentation of disease progression o Time to OS defined as the time from the date of the first administration of study drug until the date of death from any cause. Subjects who are lost to follow-up and those who are alive at the date of data cutoff will be censored at the date the subject was last known to be alive (or the data cutoff date) ? Safety o AEs, clinical laboratory values, vital signs, 12-lead ECG, Lansky Play Scores or Karnofsky Performance Status scores, physical examination findings, and bone growth and height (including proximal tibial growth plates)during treatment and follow-up ? Plasma lenvatinib exposure ? Assessment of blood or tumor biomarkers that correlate with clinical response to lenvatinib treatment or AEs associated with lenvatinib treatment Cohort 2: Efficacy o BOR over the treatment period o ORR (osteosarcoma group) o DOR o PFS o DCR defined as the percentage of subjects who have a BOR of CR or PR or SD. To be assigned a best overall response of SD, the time from the first administration of study drug until the date of documented SD should be =7 weeks. o Durable SD rate defined as the percentage of subjects who have the duration of SD lasting = 23 weeks o CBR defined as the percentage of subjects | — |
Countries
France, Germany, Italy, Spain, United Kingdom
Contacts
Public ContactMedical Information
Eisai Europe Ltd
Outcome results
None listed