Refractory or Recurrent Neuroblastoma in ChildrenPhase 2NCT04842526
Efficacy and Safety of Anlotinib, Irinotecan and Temozolomide in the Treatment of Refractory or Recurrent Neuroblastoma in Children: an Open, Single Arm, Single Center, Phase II Clinical Study
A Phase 2 study testing Anlotinib and irinotecan combined with temozolomide in people with Refractory or Recurrent Neuroblastoma in Children, run by Tianjin Medical University Cancer Institute and Hospital.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Refractory or Recurrent Neuroblastoma in Children
- What is being tested?
- Anlotinib and irinotecan combined with temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- No sites listed yet
- Study dates
- 12 Apr 2021to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Written informed consent was signed before admission;
- Under 21 years old, both male and female;
- Patients with distant metastasis or locally advanced neuroblastoma judged by the researchers to be unsuitable for surgical treatment;
- According to RECIST v1.1, at least one measurable lesion was judged by CT or MRI;
- 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;
- PS score: 0-1 (for amputees, it can be relaxed to 2); the expected survival time is more than 12 weeks;
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- At least 2 weeks after the last biotherapy and 3 weeks after the last chemotherapy;
- 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).
- 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%)
- All women of childbearing age should be given adequate contraceptive treatment before and after 7 weeks of pregnancy.
- The subjects voluntarily or their legal guardians agreed to join the study, with good compliance and follow-up of safety and survival.
Who cannot join
- Received the following treatment within 3 weeks before treatment:
- Radiotherapy, surgery, chemotherapy and molecular targeted therapy for tumors;
- Other clinical research drugs;
- Live attenuated vaccine.
- Patients who had received anti angiogenic targeted drugs in the past 3 months, such as apatinib, pazoparib, sunitinib, sorafenib, bevacizumab, imatinib, clotriminib, famitinib, anlotinib, repaglinide, endostatin, etc.
- Patients who have previously received irinotecan or combined with temozolomide for progression.
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- Surgery and / or radiotherapy for solid tumors were planned during the study period (regardless of < 5% of bone marrow areas).
- Long term unhealed wounds, ulcers or fractures, major surgery 28 days before enrollment or minor surgery 7 days before enrollment, known bleeding tendency, history of thrombosis 3 months before enrollment, cerebrovascular events, abdominal fistula, gastrointestinal perforation, abdominal abscess 6 months before enrollment, known brain metastasis.
- Severe infection (e.g. intravenous antibiotics, antifungal or antiviral drugs) occurred within 1 week before treatment, or fever of unknown origin > 38.5 ° C occurred during screening / before the first administration.
- Hypertension could not be well controlled by antihypertensive drugs (infants > 100 / 60mmhg, preschool children (< 6 years old) > 110 / 70mmhg, school-age children (6-12 years old) > 120 / 80mmHg, adolescence and adults (> 18 years old) > 140 / 90mmHg).
- There were significant clinical bleeding symptoms or clear bleeding tendency within 3 months before treatment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood + + and above, vasculitis, etc.; or arteriovenous thrombosis events within 6 months before treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism Long term anticoagulant therapy with warfarin or heparin or long-term antiplatelet therapy (aspirin ≥ 300 mg / day or clopidogrel ≥ 75 mg / day) is needed.
- There were active heart diseases, including myocardial infarction, severe / unstable angina pectoris, etc. within 6 months before treatment. The left ventricular ejection fraction (LVEF) was less than 50% and the arrhythmias were poorly controlled (including QTCF interval > 450 ms in male and > 470 MS in female).
- Any other malignant tumor was diagnosed within 3 years before treatment.
- Known to be allergic to the study drug or any of its excipients.
- Human immunodeficiency virus (HIV) infection, active hepatitis B (HBsAg positive and HBV DNA ≥ 500 IU / ml), hepatitis C (HCV antibody positive and HCV-RNA higher than the detection limit of the analytical method).
- The patients with huge tumor, easy to burst and bleeding, tumor regression, easy to lead to bleeding and other high-risk patients.
- According to the judgment of the researcher, there are concomitant diseases (such as poorly controlled hypertension, severe diabetes, neurological or mental diseases, etc.) or any other conditions that seriously endanger the safety of the subject, may confuse the results of the study, or affect the completion of the study.
About this study
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.
- Being tested
- Anlotinib and irinotecan combined with temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anlotinib and irinotecan combined with temozolomideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib and irinotecan combined with temozolomide | Experimental | Not described Receives: Drug: Anlotinib and irinotecan combined with temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
Randomization began until the first tumor progression or time of death
Measured: up to six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2021
- Study start12 Apr 2021 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory or Recurrent Neuroblastoma in ChildrenStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04842526
- Sponsor's protocol ID
- Qiang Zhao1
- Status last verified
- Feb 2021
- First submitted
- 29 Mar 2021
- Last updated
- 13 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Anlotinib, Irinotecan and Temozolomide in the Treatment of Refractory or Recurrent Neuroblastoma in Children: an Open, Single Arm, Single Center, Phase II Clinical Study
- ClinicalTrials.gov ID
- NCT04842526
- Acronym / sponsor ID
- Qiang Zhao1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Study start
- 12 Apr 2021 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 13 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anlotinib and irinotecan combined with temozolomide | Experimental | Drug: Anlotinib and irinotecan combined with temozolomide |
Who may qualify
- Ages
- 0 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (26 listed)
- Written informed consent was signed before admission;
- Under 21 years old, both male and female;
- Patients with distant metastasis or locally advanced neuroblastoma judged by the researchers to be unsuitable for surgical treatment;
- According to RECIST v1.1, at least one measurable lesion was judged by CT or MRI;
- 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;
Key exclusion criteria (17 listed)
- Received the following treatment within 3 weeks before treatment:
- Radiotherapy, surgery, chemotherapy and molecular targeted therapy for tumors;
- Other clinical research drugs;
- Live attenuated vaccine.
- Patients who had received anti angiogenic targeted drugs in the past 3 months, such as apatinib, pazoparib, sunitinib, sorafenib, bevacizumab, imatinib, clotriminib, famitinib, anlotinib, repaglinide, endostatin, etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anlotinib and irinotecan combined with temozolomideAnlotinib, 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. | Drug | Anlotinib and irinotecan combined with temozolomide |
Primary outcome
progression-free survival
Time frame: up to six months
Randomization began until the first tumor progression or time of death
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anlotinib and irinotecan combined with temozolomide in people with Refractory or Recurrent Neuroblastoma in Children, run by Tianjin Medical University Cancer Institute and Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival (time frame: up to six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2021.