Pediatric solid tumors presenting in adulthood MedDRA version: 19.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Opdivo
Product Name: Nivolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nivolumab
CAS Number: EU/1/15/1014
Current Sponsor code: BMS-936558
Other des
Sponsors
Grupo Español de Tumores Huérfanos e Infrecuentes (GETHI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be = 18 years of age, and any subjects of any gender is allowed. 2. Subjects must have histologically confirmed diagnosis of unresectable, recurrent, and/or metastatic childhood malignancies: a. Medulloblastoma b. Hepatoblastoma c. Neuroblastoma d. Wilms’ tumor e. Retinoblastoma f. Pinealoblastoma g. Pancreatoblastoma h. Askin’s tumor and Ewing family of tumors i. Langerhans cell histiocytosis j. Other pediatric malignancies: to be discussed with steering comitee. 3. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status score =2. 4. Subjects must have at least one site of measurable/evaluable disease on CT/MRI scans. Baseline imaging must be performed within 30 days of Day 1 of study. 5. Patients may have received prior standard therapy as defined by the attending physician for every tumor subtype. Cases not candidate for standard therapies will be allowed in the trial, according to the attending physician criteria. Additionally those tumors where standard therapy does not exist will be also eligible. 6. Subjects must have adequate electrolyte values, bone marrow, renal and liver functions at screening as defined below: a. WBC = 2 x 109/L b. Absolute neutrophil count (ANC) = 1.5 x 109/L c. Platelets = 100 x 109/L d. Hemoglobin = 9.0 g/dL e. Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) 40 mL/min (if using Crockcroft-Gault formula below): i. Female CrCl = (140 – age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL ii. Male CrCl = (140 – age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL f. Total Bilirubin = 2 x ULN (unless elevated secondary to benign?conditions such as Gilbert’s disease, who can have total bilirrubine < 3.0 mg/dL) g. AST and ALT = 3 x ULN (except patient with liver metastasis who can have values = 5 x ULN) 7. Subjects must be capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening study-specific procedures. 8. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. 9. Women of childbearing potential (WOCBP) must agree to use appropriate and effective method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy from Day 1 of study and for 5 months (time required for nivolumab to undergo 6,1 half-lives) after the last dose of investigational drug administration. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab and are based on the protocol requirement that WOCBP use contraception for 6,1 half-lives and men who are sexually active with WOCBP use contraception for 8,5 half-lives. Effective methods of birth control include: a. total abstinence from sexual intercourse (if it is the subject’s preferred and usual lifestyle; for beginning a minimum one complete menstrual cycle prior to study drug administration and to extend 6 months after treatment); b. vasectomized subject or partner(s); vasectomy (males); c. intr
Exclusion criteria
Exclusion criteria: 1. Subjects should be excluded if they have had prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways. 2. Subjects who are curable by conventional multidisciplinary management. 3. Subjects with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol. 4. Subjects who have received wide field radiotherapy = 4 weeks or limited field radiation for palliation 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 19. Subjects who have received a live vaccine within 30 days prio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall response rate;Secondary Objective: - Progression free survival. - Overall survival. - Disease control rate. - Duration of overall response. - Time to progression. - Time to treatment failure . - Time to objective response . - Toxicity profile of the combination of Nivolumab and Ipililumab. - Quality of life (QoL) along treatment. Translational research Objetives: - Association between PD-1 and PD-L1 expression in tumor, with the activity of nivolumab and ipilimumab combination. - Association between germline coding SNPs and regulatory SNPs with the activity of nivolumab and ipilimumab combination. -Association between tumor neoepitopes, determined through WES of tumor DNA, with clinical activity of nivolumab and ipilimumab combination. Additionally, mutational patterns in responders and non-responders will be explored. -Association between the degree of activation of lymphocytes, extracted from peripheral blood of patients in this trial, with real clinical activity of nivolumab and ipilimumab combination.;Primary end point(s): Overall response rate (ORR);Timepoint(s) of evaluation of this end point: Every 9 weeks since start o treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Continuosly through the study visits;Secondary end point(s): - Progression free survival. - Overall survival. - Disease control rate. - Duration of overall response. - Time to progression. - Time to treatment failure . - Time to objective response . - Toxicity profile of the combination of Nivolumab and Ipililumab. - Quality of life (QoL) along treatment. Translational research Objetives: - To identify molecular profiles able to predict patient response to treatment in terms of both efficacy and toxicity. | — |
Countries
Spain
Contacts
Public ContactMarta Domínguez
Dynamic Science S.L
Outcome results
None listed