Risk Factor-Guided Therapy for Neuroblastoma

Not currently recruiting at 244 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to treat young patients with non-high risk neuroblastoma, a type of cancer that mostly affects infants and toddlers. Researchers want to determine if monitoring the cancer and using treatment only when necessary can be as effective as immediate treatment. This approach might help avoid some risks and side effects of standard treatments, such as chemotherapy drugs like Carboplatin and Cyclophosphamide. Participants should be under 18 months old, have a recent diagnosis of neuroblastoma, and not have undergone prior treatment other than certain medications like dexamethasone. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this study have varying safety levels, with some known risks.

Carboplatin, a chemotherapy drug, can harm the kidneys, especially when combined with certain other medications. It may also cause nausea and lower blood counts, leading to infections.

Cyclophosphamide is generally safe for adults and children. However, it can cause cancer and birth defects, so it requires careful use in pregnant women.

Doxorubicin hydrochloride can increase the risk of heart failure, which might occur during treatment or even years later. It can also cause severe skin damage if it leaks from the vein during administration.

Etoposide might cause serious allergic reactions and can significantly lower blood cell counts, increasing the risk of infections.

These treatments are commonly used in cancer therapy. Despite their side effects, they have been used safely in many patients. It is important to consult a healthcare provider to understand the risks and benefits for each specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a risk factor-guided approach to treating neuroblastoma, potentially offering a more personalized treatment strategy. Unlike the standard of care, which typically involves a one-size-fits-all aggressive chemotherapy regimen, this approach tailors treatment intensity based on the patient's risk level. The trial examines if some patients can achieve similar outcomes with less intensive treatment, like extended clinical observation, while still utilizing potent chemotherapy drugs such as carboplatin, etoposide, cyclophosphamide, and doxorubicin hydrochloride as needed. This could mean fewer side effects and a better quality of life for patients who don't need immediate aggressive treatment.

What evidence suggests that this trial's treatments could be effective for non-high risk neuroblastoma?

In this trial, participants may receive different treatments based on their assigned group. Research has shown that carboplatin, part of the chemotherapy regimen in Groups B and C, effectively fights neuroblastoma by stopping cell growth. Cyclophosphamide, also used in these groups, affects the immune system and has shown good results when combined with other drugs. Doxorubicin, included in the chemotherapy regimen, slows cell growth and causes cancer cells to die, aiding in neuroblastoma treatment. Etoposide, another chemotherapy component, helps patients achieve remission, preventing cancer recurrence. Together, these treatments have shown promise in managing neuroblastoma, especially when the cancer is not very aggressive. ^{3 6 7 8 9}

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 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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8040674/

Phase II investigational window using carboplatin, iproplatin ... Results: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial ...

2. siope.eu siope.eu/media/documents/escp-high-risk-neuroblastoma-standard-clinical-practice-recommendations.pdf

escp-high-risk-neuroblastoma-standard-clinical-practice- ... The initial results reported by MSKCC (overall CR/VGPR of 83%) have not been replicated by 2 randomized studies conducted by the French (SFOP) and Austrian ...

3. ascopubs.org ascopubs.org/doi/10.1200/EDBK_349783

High-Risk and Relapsed Neuroblastoma: Toward More ... Patients treated during this trial had a 97% end-induction response rate and a 73.7% 3-year EFS rate, both of which compare favorably to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7586261/

The Inhibitory Effect of Carboplatin Injection on Human ... The results in all these aspects showed that carboplatin injection had a significant inhibitory effect on neuroblastoma SK-N-SH. Literature review found that ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01526603

High Dose Chemotherapy and Autologous Transplant for ... This is a standard of care document, outlining the therapy for children with high risk neuroblastoma who are not eligible for Children's Oncology Group (COG) ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/020452s005lbl.pdf

PARAPLATIN Label CLINICAL PHARMACOLOGY. Carboplatin, like cisplatin, produces predominantly interstrand DNA cross-links rather than DNA-protein cross-links.

7. mayoclinic.org mayoclinic.org/drugs-supplements/carboplatin-intravenous-route/description/drg-20062578

Carboplatin (intravenous route) - Side effects & uses Carboplatin is an antineoplastic agent (cancer medicine). It interferes with the growth of cancer cells, which are eventually destroyed by the ...

8. jnccn.org jnccn.org/view/journals/jnccn/22/6/article-p413.xml?print

Neuroblastoma, Version 2.2024, NCCN Clinical Practice ... As robust safety and efficacy data are not yet available to support these approaches, the panel does not recommend adoption of these ...

9. drugs.com drugs.com/carboplatin.html

Carboplatin: Use, Dosage, Side Effects, Warnings Carboplatin can harm your kidneys, especially if you also use certain medicines for infections, cancer, osteoporosis, organ transplant rejection ...