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)MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003352-67-IT
- Lead Sponsor
- EISAI LIMITED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 111
1. Age: =12 months to <18 years old at the time of ICF. >6 months and <12 months at the times of ICF pts will be enrolled one dose level behind he dose level at which the =12 months to <18 years old group are enrolled.2. Diagnosis: Ph 1: Histologically confirmed solid tumor, excluding CNS tumor, which is relapsed or refractory, and for which there are no currently available therapies. Ph 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:Ph 1: Pts must have either measurable or evaluable disease as per RECIST 1.1. Ph 2: Pts 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 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: Pt’s current disease state must be one for which there is no known curative therapy.5. Performance level: Performance score =50% KPS or Lansky.6. Pts must have fully recovered from the acute toxic effects of all prior anticancer treatments prior to study drug admin:• Myelosuppressive chemotherapy: Must not have received within 21 days to study drug admin Hematopoietic growth factors: Must not have received a long-acting growth factor within 14 days or a short-acting factor within 7 days. For agents that have known AEs occurring beyond 7 days after admin, 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:Must not have received an antineoplastic targeted therapy within 14 days. For agents that have known AEs occurring beyond 14 days after admin, 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 Ab.• XRT: Must not have received within 14 days prior to study drug admin 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 admin. • 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 admin.7. Adequate bone marrow function, defined as:• ANC =1 × 109/L.• Platelet count =100 × 109/L.• Hb at least 8.0 g/dL at baseline As blood transfusions are permitted to meet the hemoglobin criteria, pts must not be known to be refractory to red blood cell or platelet transfusions. 8. Adequate renal function, defined as:• A serum creatinine based on age/gender, derived from the Schwartz formula for estimating GFR. Refer to table in protocol.• GFR =50ml/min/1.73m2, based on a 12 or 24h urine creatinine collection. 9. Adequate liver function, defined as:• Bilirubin (sum of conjugated + unconjugated) =1.5 times the ULN for age.• Alkaline phosphatase, ALT and AST =3 × ULN, unless there ar
1. Pregnancy, breastfeeding, contraception: Females who are breastfeeding or pregnant at Screening or Baseline. 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 IUD or 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: Pt receiving corticosteroids who have not been on a stable dose for at least 7 days prior to study drug administration. Anticancer agents: Pt who are currently receiving other anticancer agents. Anti-GVHD agents post-transplant: Pt who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant. Strong CYP3A4 inducers/inhibitors.
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.
4. Any malignancy that required treatment, 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 (*
Pt 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: Pt with known congestive heart failure, symptomatic or LV ejection fraction <50% or shortening fraction <27% and pt with congenital long QT syndrome, bradyarrhythmias, or QTc >480 msec on at least 2 separate ECGs.
9. Has CNS disease: Pt with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy and have discontinued the use of corticosteroids for this indication for at least 28 days prior to study drug administration. Pt must be clinically stable. It is not the intention of this protocol to treat pt with active brain metastases.
10. Have had or are planning to have the following invasive procedures: Major surgical procedure or significant traumatic injury within 28 days prior to study drug administration. Laparoscopic procedure or open biopsy within 7 days prior to study drug administration. Central line placement or subcutaneous port placement is not considered major
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