Neuroblastoma
Conditions
Keywords
Neuroblastoma, Arsenic Trioxide, Children
Brief summary
This clinical trial aims to explore and evaluate the efficacy and safety of combined chemotherapy with arsenic trioxide for stage 4/M neuroblastoma.
Detailed description
This study is a prospective, single-arm, open-lable, multi-center clinical trial. Children≤ 14 years old are eligible for this study if they were newly diagnosed with neuroblastoma and assessed as stage 4 according to the International Neuroblastoma Staging System (INSS) or stage M according to the International Neuroblastoma Risk Group (INRG) respectively. Patients enrolled in this study will receive combined induction chemotherapy with arsenic trioxide following an modifed protocol based on N7 and NB2004 protocols. Objective response rate (ORR) at 4 weeks after completing induction chemotherapy was defined as the main outcome and adverse events were monitored and graded in the meantime.
Interventions
DRUGArsenic Trioxide
Arsenic trioxide（ATO） is administered 0.16mg/kg per day over eight hours IV daily for ten days. Patients will receive ATO alone on days 1-2 and combined with conventional induction chemotherapy on days 3-10. Nine cycles at most of ATO-combined chemotherapy were applied in the whole scheme.
Sponsors
Yang Li
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Combined induction chemotherapy with arsenic trioxide
Eligibility
Sex/Gender
ALL
Age
No minimum to 14 Years
Healthy volunteers
No
Inclusion criteria
1. Untreated Stage 4/M neuroblastoma patients according to the International Neuroblastoma Staging System（INSS) or the International Neuroblastoma Risk Group (INRG) staging system; 2. Patients not more than 14 years old; 3. There are measurable lesions; 4. Guardians agreed and signed informed consent.
Exclusion criteria
1. Patients who had suffered from other tumors and received chemotherapy or abdominal radiotherapy. 2. Patients with one or more critical organs failure such as heart, brain, kidney failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Four weeks after ATO-combined induction chemotherapy | The percentage of patients who had complete remission（CR）or partial remission（PR）after induction chemotherapy combined ATO. Per Response Evaluation Criteria In Solid Tumors Criteria (WHO criteria) for target lesions and assessed by MRI or CT: CR: All lesions completely disappear, maintained for at least 4 weeks. PR: Estimated tumor size reduction by more than 50%, maintained for at least 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | 3 years. | The proportion of patients who are alive from the date of randomization to 3 years, regardless of the cause of death. |
| Progression Free Survival Rate | 3 years. | The proportion of patients who have not experienced progression or death from any cause, whichever occurs first, within a maximum of 3 years from the date of enrollment. Treatment response was evaluated according to the WHO criteria for the efficacy of solid tumours, which was classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). PD was characterized as more than 25% increase in one or more lesions or appearance of new lesions. |
| Number of Participants With Adverse Events | From date of ATO-combined chemotherapy until the date of first documented adverse event, and follow up for 3 years. | Adverse events are monitored and graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) |
Countries
China
Participant flow
Recruitment details
Until July 31, 2023, a total of 80 children from the paediatrics departments of 8 hospitals, were recreated in this study.
Pre-assignment details
6 patients changed therapeutic regimen，7 patient withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| ATO-combined Chemotherapy Patients receive combined induction chemotherapy with arsenic trioxide.
Arsenic Trioxide: Arsenic trioxide（ATO） is administered 0.16mg/kg per day over eight hours IV daily for ten days. Patients will receive ATO alone on days 1-2 and combined with conventional induction chemotherapy on days 3-10. Nine cycles at most of ATO-combined chemotherapy were applied in the whole scheme. | 67 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 6 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | ATO-combined Chemotherapy |
|---|---|
| Age, Continuous | 3.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment China | 67 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 67 |
| other Total, other adverse events | 67 / 67 |
| serious Total, serious adverse events | 0 / 67 |
Outcome results
Primary
Objective Response Rate
The percentage of patients who had complete remission（CR）or partial remission（PR）after induction chemotherapy combined ATO. Per Response Evaluation Criteria In Solid Tumors Criteria (WHO criteria) for target lesions and assessed by MRI or CT: CR: All lesions completely disappear, maintained for at least 4 weeks. PR: Estimated tumor size reduction by more than 50%, maintained for at least 4 weeks.
Time frame: Four weeks after ATO-combined induction chemotherapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATO-combined Chemotherapy | Objective Response Rate | 62 Participants |
Secondary
Number of Participants With Adverse Events
Adverse events are monitored and graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Time frame: From date of ATO-combined chemotherapy until the date of first documented adverse event, and follow up for 3 years.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATO-combined Chemotherapy | Number of Participants With Adverse Events | 60 Participants |
| Vomiting | Number of Participants With Adverse Events | 33 Participants |
| Transaminitis | Number of Participants With Adverse Events | 4 Participants |
| Cardiovascular Toxicity | Number of Participants With Adverse Events | 1 Participants |
| Infection | Number of Participants With Adverse Events | 20 Participants |
Secondary
Overall Survival Rate
The proportion of patients who are alive from the date of randomization to 3 years, regardless of the cause of death.
Time frame: 3 years.
Population: 1 patient lost to follow-up for OS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATO-combined Chemotherapy | Overall Survival Rate | 68.0 percentage of participent |
Secondary
Progression Free Survival Rate
The proportion of patients who have not experienced progression or death from any cause, whichever occurs first, within a maximum of 3 years from the date of enrollment. Treatment response was evaluated according to the WHO criteria for the efficacy of solid tumours, which was classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). PD was characterized as more than 25% increase in one or more lesions or appearance of new lesions.
Time frame: 3 years.
Population: 6 patients lost to follow-up for PFS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ATO-combined Chemotherapy | Progression Free Survival Rate | 47.7 percentage of participent |