Phase 1: Relapse and refractory pediatric solid tumor, Phase 2: Relapse and refractory neuroblastoma
Conditions
Interventions
investigational material(s)
Generic name etc : OP-09
INN of investigational material : Tamibarotene
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigationa
Sponsors
Osaka City General Hospital, Junichi Hara
Kyushu University Hospital
National Cancer Center Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Aged 3 to 30 years old at study entry 2) Phase 1:Histologically proven either sarcoma, blastoma, germ cell tumors, or central nervous system tumor except malignant lymphoma Phase 2:Histologically proven neuroblastoma and experienced high-dose chemotherapy with an autologous hematopoietic stem cell transplantation 3) More than one regimen of chemotherapy including standard therapeutic agents(Patients without options of the standard treatment) 4) Found a lesion by either imaging inspection, bone marrow examination, or tumor marker diagnosis(It doesn't matter whether the presence or absence of measurable lesions defined by RECIST but remission cases are not targeted) 5) PS(Karnofsky or Lansky)>=50% 6) The periods as below have passed since the last use of anti-tumor agents (1) 7 days or more have passed if dosing method which is continuously-administered more than once in 3 days with no rest period (2) 14 days or more have passed if other dose methods were used 7) The periods as below have passed since the last irradiation date a) 12 weeks or more if radiation fields contain either whole brain and spine, whole abdomen, whole lung, whole body, or more than 50% of pelvis b) 14 days or more if irradiation fields contain less than 3 vertebrae and localized irradiation to other fields c) 6 weeks or more if irradiation fields are none of the above applies 8) No difficulty to take a soft capsule or a tablet 9) Clinical data within 14 days (1) Neutrophil count>=1500/mm3(no administration of G-CSF within 3 days before blood-collecting) (2) Platelet count>=7.5x10^4/mm3(no blood transfusion within 3 days before blood-collecting) (3) Total bilirubin<=1.5mg/dl (4) AST(GOT)<=100U/L (5) ALT(GPT)<=100U/L (6) TG<=300mg/dl (7) Serum creatinine(Cre)<=ULN of children reference value x3(no dialysis) (8) Hemoglobin(Hb)A1c<=6.2%(NGSP) 10) No abnormalities which require an intervention in 12-lead electrocardiogram tested within 28 days before the study entry 11) Written informed consent from a patient and/or a legal guardian
Exclusion criteria
Exclusion criteria: 1) Synchronous cancer and asynchronous cancer with 5 years of disease-free survival except carcinoma in situ or intramucosal carcinoma 2) In patients having a brain tumor or metastasis to brain, a symptom with the intracranial hypertension is poor in control 3) Active infection requires systemic treatment 4) Respiratory failure requiring oxygen administration 5) Medical history and complication of thrombosis 6) Woman who are or may be pregnancy, or are impossible to use effective methods of contraception from 1 month prior to the administration to 2 years after the final dose of treatment. Woman with impossible to discontinue breast-feeding from 1 month prior to the administration to 2 years after the final dose of treatment. Men who are impossible to use effective methods of contraception during the administration and 6 months after the final dose of treatment. 7) Patients considered to be difficult to participate because of psychiatric illness or complication of psychological symptom 8) Patients with history of hypersensitivity to the study drugs 9) Patients otherwise considered to be ineligible for enrollment in the study by an investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety efficacy exploratory pharmacokinetics Phase 1:Event rate of dose-limiting toxicity by using tamibarotene and decitabine combination, Phase 2:Progression Free Survival Phase 1:8 courses completed or discontinuation of the protocol treatment(CTCAE v.4.0), Phase 2:1 year after first administration of last case, completion or discontinuation of the protocol treatment(RECIST v1.1) | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy exploratory pharmacokinetics Response Rate, Clinical Benefit Rate, Adverse event rate, Pharmacokinetics, Overall survival rate in only Phase 2 Phase 1:8 courses completed or discontinuation of the protocol treatment, Phase 2:1 year after first administration of last case, completion or discontinuation of the protocol treatment | — |
Countries
Japan
Outcome results
None listed