Risk Factor-Guided Therapy for Neuroblastoma

Recruiting at 233 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: MYCN amplified tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Variable, up to 8 courses

621 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow the use of dexamethasone. It's best to discuss your specific medications with the trial team.

Is the treatment for neuroblastoma generally safe in humans?

The treatment involving drugs like carboplatin, etoposide, and cisplatin has been studied for safety in humans. Common side effects include vomiting, bone marrow toxicity (which affects blood cell production), and hearing loss, but these are generally manageable with careful monitoring. There were no treatment-related deaths in some studies, indicating that the treatment can be safe if supervised properly. ^{1 2 3 4 5}

How is the drug combination of carboplatin, cyclophosphamide, doxorubicin, and etoposide unique for treating neuroblastoma?

This drug combination is unique because it uses carboplatin and etoposide as alternatives to cisplatin, aiming to reduce toxicity while still being effective against neuroblastoma. It offers a different approach by combining these drugs to potentially improve outcomes for patients with this condition. ^{1 3 5 6 7}

What data supports the effectiveness of the drugs used in the Risk Factor-Guided Therapy for Neuroblastoma?

Research shows that drugs like etoposide, carboplatin, and cyclophosphamide have been effective in treating neuroblastoma, with studies indicating good response rates in patients. Additionally, combinations of these drugs with others like doxorubicin have shown improved outcomes in advanced neuroblastoma cases. ^{1 3 4 6 8}

Who Is on the Research Team?

Holly J Meany

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with non-high risk neuroblastoma or ganglioneuroblastoma. Eligible participants are under 18 months old, have specific tumor sizes and locations, and must not have received prior cancer treatment except dexamethasone. They should also exhibit certain genomic features without MYCN gene amplification.

Inclusion Criteria

My cancer's genetic features match one of the study's treatment groups.

My largest tumor is smaller than 5 cm, and I haven't had it removed or biopsied.

My baby is under 6 months old with a small adrenal tumor.

Exclusion Criteria

Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure

My tumor has MYCN amplification.

Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Patients undergo clinical observation for 96 weeks in Group A or 3 years in Groups B and C in the absence of disease progression. Imaging studies such as CT, MRI, and/or ultrasound are conducted throughout the trial.

96 weeks to 3 years

Treatment

Upon disease progression, patients in Groups B and C receive first-line chemotherapy comprising carboplatin, etoposide, cyclophosphamide, and doxorubicin hydrochloride. Treatment repeats every 21 days for 2-8 courses.

Variable, up to 8 courses

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes annual assessments for up to 10 years post-enrollment.

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Clinical Observation
• Cyclophosphamide
• Doxorubicin Hydrochloride
• Etoposide
• Laboratory Biomarker Analysis
• Pharmacological Study

Trial Overview The study tests observation versus intervention based on the progression of tumors in young patients with neuroblastoma. It aims to determine when and what treatment might be necessary by examining biomarkers within tumor cells to guide therapy decisions.

How Is the Trial Designed?

Group I: Group C (clinical observation, first-line chemotherapy) Experimental Treatment 11 Interventions

Patients at high risk for deterioration and a poor outcome immediately receive first-line chemotherapy as in Group B. All other patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients receive first-line chemotherapy as in Group B. Once a PR or better is achieved, patients undergo clinical observation for 3 years. Patients also undergo CT, MRI, and/or ultrasound throughout the trial and undergo bone marrow aspiration, bone marrow biopsy, and tumor biopsy at screening and time of progression.

Group II: Group B (clinical observation, first-line chemotherapy) Experimental Treatment 11 Interventions

Patients undergo clinical observation for 3 years in the absence of disease progression. Upon disease progression, patients undergo surgery or receive first-line chemotherapy comprising carboplatin IV over 1 hour on day 1 (courses 1, 2, 4, 6, and 7), etoposide IV over 1 hour on days 1-3 (courses 1, 3, 4, 5, and 7), cyclophosphamide IV over 1 hour on day 1 (courses 2, 3, 5, 6, and 8), and doxorubicin hydrochloride IV over 15 minutes on day 1 (courses 2, 4, 6 and 8). Treatment with chemotherapy repeats every 21 days for 2-8 courses in the absence of disease progression or unacceptable toxicity. Once a PR or better is achieved, patients undergo clinical observation for 3 years. Patients also undergo CT, MRI, and/or ultrasound throughout the trial and undergo bone marrow aspiration, bone marrow biopsy, and tumor biopsy at screening and time of progression.

Group III: Group A (clinical observation) Experimental Treatment 4 Interventions

Patients undergo clinical observation for 96 weeks in the absence of disease progression. Patients also undergo CT, MRI, and/or ultrasound throughout the trial.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase II study involving 47 children with metastatic neuroblastoma, the combination of etoposide and carboplatin showed a 43% response rate, including 4 complete remissions and 13 partial remissions, indicating potential efficacy as an alternative treatment.

The treatment was associated with significant hematologic toxicity, leading to a median delay of 39 days between courses, and some patients experienced notable kidney and hearing side effects, suggesting the need for careful monitoring and further evaluation in newly diagnosed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study. Frappaz, D., Michon, J., Hartmann, O., et al.[2017]

In a study of 42 children with newly diagnosed stage III or IV neuroblastoma, the OPEC chemotherapy regimen resulted in a good partial response in 74% of patients, with an even higher response rate of 78% among those who strictly followed the treatment protocol.

The OPEC regimen was found to be at least as effective as the more toxic OPEC-D regimen, with significantly lower treatment-related complications, suggesting it could be a safer alternative for treating advanced neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26. Shafford, EA., Rogers, DW., Pritchard, J.[2017]

In a study involving 13 children with refractory neuroblastoma, the treatment with the epipodophyllotoxin VM-26 resulted in partial responses in 3 patients, indicating its potential efficacy in reducing tumor size and tumor cell presence in bone marrow.

The treatment was associated with minimal acute nonhematologic toxicity, although hematologic toxicity was difficult to assess due to pre-existing bone marrow involvement from the tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epipodophyllotoxin VM-26 in the treatment of childhood neuroblastoma. Rivera, G., Green, A., Hayes, A., et al.[2013]

In a study comparing high-dose chemotherapy regimens for high-risk neuroblastoma in Egypt and the United States, patients in Egypt experienced delayed engraftment and higher rates of severe complications, particularly sinusoidal obstruction syndrome, linked to pre-existing hepatitis infections.

Despite these challenges, the study concluded that autologous stem-cell transplantation is feasible in resource-limited settings, highlighting the need for careful management of patient comorbidities and treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources. Elzembely, MM., Park, JR., Riad, KF., et al.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II study of cisplatinum and carboplatinum (CACIS) combination in advanced stage neuroblastomas. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Epipodophyllotoxin VM-26 in the treatment of childhood neuroblastoma. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Murine neuroblastoma: further evaluation of the C1300 model with single antitumor agents. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Very-high-dose cisplatin and etoposide in children with untreated advanced neuroblastoma. [2017]

7. Japan pubmed.ncbi.nlm.nih.gov

[Effectiveness of cis-dichlorodiammine-platinum in the treatment of advanced neuroblastoma]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources. [2019]