Refractory or Recurrent Neuroblastoma in Children
Conditions
Brief summary
Neuroblastoma is an embryonal tumor originated from primitive neural crest cells. It is the most common extracranial solid tumor in children. It is characterized by abundant blood vessels, rapid growth and early metastasis.With the gradual improvement of diagnosis and treatment technology, the survival rate of children with Neuroblastoma in China has been increasing year by year, but the Overall Survival is still lower than that in European and American countries, so new and efficient treatment methods are urgently needed in clinical practice.Anti-angiogenesis target therapy is an important component of the malignant tumor treatment, hydrochloric acid for Anlotinib has the anti-tumor angiogenesis and suppress tumor growth, Anlotinib currently in thyroid carcinoma, esophageal cancer, liver cancer, colorectal cancer, soft nest, cervical cancer, soft tissue sarcoma and so on the many kinds of cancer are conducting clinical trials, but in neuroblastoma application has not been reported.The purpose of this study was to explore the therapeutic effect and mechanism of Anlotinib and irinotecan combined with temozolomide in the treatment of refractory or recurrent Neuroblastoma in children.Neuroblastoma is an embryonal tumor originated from primitive neural crest cells. It is the most common extracranial solid tumor in children. It is characterized by abundant blood vessels, rapid growth and early metastasis.It accounts for 8%-10% of all malignant tumors in children, with an annual incidence of 0.3-5.5/100,000.The prognosis of Neuroblastoma was closely related to age at diagnosis, clinical stage, tumor pathological type, N-myc gene copy number and DNA index.According to the above five indicators, the Children's Oncology Group divided NB into low, medium and high risk groups.According to the 2013 Children's Oncology Group data, the current 5-year Overall Survival of low - and moderate-risk Neuroblastoma patients was 90%, while the Overall Survival of high-risk patients was only 50%.The current treatment of Neuroblastoma is a multidisciplinary combination of surgery, chemoradiotherapy and autologous stem cell transplantation.With the gradual improvement of diagnosis and treatment technology, the survival rate of children with NB in China has been increasing year by year, but the Overall Survival is still lower than that in European and American countries, so new and efficient treatment methods are urgently needed in clinical practice.
Interventions
DRUGAnlotinib and irinotecan combined with temozolomide
Anlotinib, 7mg/m2, PO, was given for 14 days and stopped for 7 days; Irinotecan, 50mg/m2, D1-5, IV; Temozolomide, 100mg/m2, d1-5, PO; Three weeks is a cycle.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent was signed before admission; 2. Under 21 years old, both male and female; 3. Patients with distant metastasis or locally advanced neuroblastoma judged by the researchers to be unsuitable for surgical treatment; 4. According to RECIST v1.1, at least one measurable lesion was judged by CT or MRI; 5. Patients who have used at least one chemotherapy regimen (including anthracycline) for treatment and are evaluated as disease progression or intolerable according to RECIST 1.1; 6. PS score: 0-1 (for amputees, it can be relaxed to 2); the expected survival time is more than 12 weeks; 7. At least 2 weeks after the last biotherapy and 3 weeks after the last chemotherapy; 8. All acute toxicity reactions caused by previous anti-tumor therapy or surgery were alleviated to 0-1 level before the screening period (according to NCI CTCAE 5.0) or to the level specified by the inclusion /
Exclusion criteria
(except for the toxicity of alopecia, etc., which was considered by the researchers to have no safety risk to the subjects). 9. Adequate organ and bone marrow functions are defined as follows: routine blood test Neutrophil count (ANC) ≥ 1000 / mm3 (1.0 × 109 / L); Platelet count (PLT) ≥ 70000 / mm3 (70 × 109 / L); Hemoglobin (HB) ≥ 7.5 g / dl (75 g / L); Blood biochemistry Serum creatinine (CR) ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance rate (cockroft Gault) Total bilirubin (TBIL) ≤ 1.5 × ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 × ULN, liver metastasis subjects should be ≤ 5 × ULN; Coagulation function International normalized ratio (INR) ≤ 1.5, prothrombin time (PT) and activated partial thromboplastin （APTT）≤1.5×ULN； urinalysis Urinary protein \< 2 +; if urinary protein ≥ 2 +, 24-hour urinary protein quantitative display protein must be ≤ 1g; Cardiac function Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%) 10. All women of childbearing age should be given adequate contraceptive treatment before and after 7 weeks of pregnancy. 11. The subjects voluntarily or their legal guardians agreed to join the study, with good compliance and follow-up of safety and survival.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival | up to six months | Randomization began until the first tumor progression or time of death |
Outcome results
None listed