DACTBT-P1/P2

JRCT ID: jRCT2051190055

Registered date:01/10/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Phase 1: Relapse and refractory pediatric solid tumor, Phase 2: Relapse and refractory neuroblastoma
• Date of first enrollment: 23/08/2018
• Target sample size: 57
• Study type: Interventional
• Intervention(s): To estimate a maximum tolerated dose and determine a recommended dose of decitabine in patients with relapse and refractory pediatric solid tumor in Phase 1 study under a recommended dose of tamibarotene which was determined in the single-agent study of tamibarotene. To evaluate safety and efficacy of tamibarotene and decitabine with a recommended dose in patients with relapse and refractory neuroblastoma in Phase 2.

Outcome(s)

• Primary Outcome: Phase 1:Event rate of dose-limiting toxicity by using tamibarotene and decitabine combination, Phase 2:Progression Free Survival
• Secondary Outcome: Response Rate, Clinical Benefit Rate, Adverse event rate, Pharmacokinetics, Overall survival rate in only Phase 2

Key inclusion & exclusion criteria

• Age minimum: >= 3age old
• Age maximum: <= 30age old
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Hara Junichi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development
• Secondary ID(s): JMA-IIA00376,JapicCTI-184066