A Phase 1 and 2 trial studying how well a combination of eribulin mesilate and irinotecan works in children with different types of cancer that are not responding to treatment or have reappeared following an initial recovery. The aim of the study is to find out how safe and effective the drug combination is in this treating this types of cancer.
- Conditions
- Phase 1: paediatric subjects with relapsed/refractory solid tumors (excluding CNS)Phase 2: paediatric subjects with relapsed/refractory rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) and Ewing sarcoma (EWS)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003352-67-PL
- Lead Sponsor
- Eisai Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1. Age: =12 months to =25 years old at the time of consent (no more
than 25% of subjects between the ages of 18 and 25 years will be
enrolled in this study).b) Phase 1,>6 months and <12 months at the times of consent (Phase 1 and Schedule A only) subjects will be enrolled one dose level behind he dose level at which the =12 months to <18 years old group are enrolled.
2. Diagnosis:
Phase 1: Histologically confirmed solid tumor, excluding CNS tumor, which is relapsed or refractory, and for which there are no currently available therapies.
Phase 2: Histologically confirmed RMS, NRSTS or EWS which is relapsed or refractory having received at least 1 prior therapy), including primary treatment.
3. Disease status:
Phase 1: Subjects must have either measurable or evaluable disease as per RECIST 1.1.
Phase 2: Subjects must have measurable disease as per RECIST 1.1.
Measurable disease is defined as meeting the following criteria:
a. 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 that is serially measurable according to RECIST 1.1 using computed tomography/magnetic resonance imaging (CT/MRI).
b. Lesions that have had radiotherapy must show subsequent radiographic evidence of increase in size by at least 20% to be deemed a target lesion.
4. Therapeutic options: Subject’s current disease state must be one for which there is no known curative therapy.
5. Performance level: Performance score =50% Karnofsky (for subjects >16 years of age) or Lansky (for subjects =16 years of age).
6. Subjects must have fully recovered from the acute toxic effects of all prior anticancer treatments prior to study drug administration:
• Myelosuppressive chemotherapy: Must not have received within 21 days to study drug administration (42 days if prior nitrosourea).
• Hematopoietic growth factors: Must not have received a long-acting growth factor (eg, Neulasta) within 14 days or a short-acting factor within 7 days. For agents that have known AEs occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor.
• Targeted therapy (antineoplastic agent eg, tyrosine kinase inhibitor): Must not have received an antineoplastic targeted therapy within 14 days. For agents that have known AEs occurring beyond 14 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the sponsor.
• Immunotherapy: Must not have received immunotherapy, e.g. tumor vaccines, within 42 days.
• Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
• Radiotherapy (XRT): Must not have received within 14 days prior to study drug administration (small field) or 42 days for craniospinal XRT, or if =50% radiation of pelvis.
• Autologous Stem cell infusion: At least 84 days must have elapsed after stem cell infusion prior to study drug administration.
• Allogeneic bone marrow transplant, including mini-transplant: No evidence of active Graft vs. Host disease and at least 100 days must have elapsed after transplant or stem cell infusion prior to study drug administration.
7. Adequate bone marrow function, defined as:
• Peripheral absolute neutrophil count (ANC) =1 × 109/L.
• Platelet count =100 × 109/L (transfusion independent,
1. Pregnancy, breastfeeding, contraception: Females who are
breastfeeding or pregnant at Screening or Baseline (as documented by a
positive beta-human chorionic [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:
? Do not agree to use a highly effective method of contraception for the
entire study period and for 6 months after study drug discontinuation, ie:
? Total abstinence (if it is their preferred and usual lifestyle)
? An intrauterine device (IUD) or intrauterine system (IUS)
? A contraceptive implant
? an oral contraceptive**
OR
? Do not have a vasectomized partner with confirmed azoospermia.
*All post pubertal females will be considered to be of childbearing
potential unless they have early menopause (amenorrheic for at least 12
consecutive months, in the appropriate age group, and without other
known or suspected cause) or have been sterilized surgically (ie,
bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all
with surgery at least 1 month before dosing).
**Must be on a stable dose of the same oral hormonal contraceptive
product for at least 4 weeks before dosing with study drug and for the duration of the study and for 6 months after study drug discontinuation.
2. Concomitant Medications:
? Corticosteroids: Subjects receiving corticosteroids who have not been
on a stable dose for at least 7 days prior to study drug administration.
? Anticancer agents: Subjects who are currently receiving other
anticancer agents.
? Anti-GVHD agents post-transplant: Subjects who are receiving
cyclosporine, tacrolimus or other agents to prevent graft-versus-host
disease post bone marrow transplant.
? Strong CYP3A4 inducers/inhibitors, including traditional herbal
medicinal products (eg St. John's Wort).
3. Prior Therapies:
? Phase 1: Received prior therapy with eribulin mesilate within 6 months
prior to study drug administration.
? Phase 2: Received prior therapies with eribulin mesilate or irinotecan
hydrochloride (IH) (for prior IH subjects can be included if there was no
tumor progression during IH therapy).
4. Any malignancy that required treatment (except for non-melanoma
skin cancer, or histologically confirmed complete excision of carcinoma
in situ), within 2 years prior to study drug administration.
5. Has hypersensitivity to either study drug or any of the excipients.
6. Has a known prior history of viral hepatitis (B or C) as demonstrated
by positive serology (presence of antigens) or have an uncontrolled
infection requiring treatment (* Subjects with a known prior history of
hepatitis B or C may be eligible pending agreement with the sponsor).
7. Has > Grade 1 peripheral sensory neuropathy or > Grade 1 peripheral
motor neuropathy graded according to the Modified (Balis) Pediatric
Scale of Peripheral Neuropathies.
8. Has cardiac pathology, defined as:
? Subjects with known congestive heart failure, symptomatic or LV
ejection fraction <50% or shortening fraction <27% and subjects with
congenital long QT syndrome,bradyarrhythmias, or QTc >480 msec on at
least 2 separate ECGs.
9. Has CNS disease: Subjects with brain or subdural metastases are not
eligible unless the metastases are asymptomatic and do not require
treatment or have been adequatel
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