Advanced Therapy for Neuroblastoma

(PEDS-PLAN Trial)

Recruiting at 28 trial locations

Overseen By Michael Isakoff, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Giselle Sholler

Must not be taking: Investigational drugs

Disqualifiers: Lactating, Malabsorption, Mental illness, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for high-risk neuroblastoma, a cancer that mostly affects children. The researchers aim to determine if adding DFMO (Eflornithine) to standard immunotherapy can improve outcomes. Participants will receive one of four possible drugs based on their specific tumor characteristics, followed by standard immunotherapy, and then DFMO for maintenance. This trial suits those with a confirmed diagnosis of high-risk neuroblastoma, who have not undergone extensive prior treatment, and meet specific health criteria. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in neuroblastoma treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on any investigational drugs at the same time as this trial.

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

Earlier studies found dasatinib safe for children. It was well tolerated at doses up to 120 mg/m², with no maximum safe dose identified. Common side effects included lower blood cell counts, headaches, and tiredness.

Research has shown that sorafenib is also safe, with fewer side effects than traditional chemotherapy.

Vorinostat has been tested in both adults and children and generally maintains a good safety record. Some serious outcomes occurred, but they were unrelated to the drug.

DFMO, used after immunotherapy in other studies, was linked to improved survival without serious safety concerns.

These findings suggest that the treatments under study are generally well-tolerated, but individual reactions can vary. Always discuss potential risks with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for neuroblastoma, like chemotherapy and radiation, target cancer cells broadly, often affecting healthy cells too. However, the treatments under investigation, including ceritinib, dasatinib, sorafenib, and vorinostat, are chosen based on the molecular profile of each patient's cancer, making them more targeted. Researchers are particularly excited about the addition of DFMO, which is given continuously for two years after standard immunotherapy. DFMO works by depleting polyamines, essential molecules that cancer cells need to grow, potentially reducing the risk of relapse. This personalized and prolonged approach aims to enhance effectiveness and improve long-term outcomes for patients.

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

Research has shown that the treatments under study for neuroblastoma offer varying levels of promise. In this trial, participants will receive one of the following drugs based on molecular-guided results: Ceritinib, Dasatinib, Sorafenib, or Vorinostat. When combined with other drugs, Ceritinib has improved outcomes for patients with high-risk neuroblastoma. Lab studies have demonstrated that Dasatinib can slow neuroblastoma growth, suggesting potential effectiveness in patients. Sorafenib targets both cancer cells and the blood vessels that support tumor growth, though its effectiveness varies. Vorinostat, when used with other treatments, has reduced tumor sizes in animal studies.

Participants in this trial will also receive standard immunotherapy, and some will receive DFMO (eflornithine) as part of their treatment regimen. DFMO has improved survival rates in patients with high-risk neuroblastoma, making it a promising option for preventing cancer recurrence. Each treatment works differently, and clinical studies continue to explore their potential benefits. ^{2 3 6 7 8}

Who Is on the Research Team?

Giselle Sholler, MD

Principal Investigator

Beat Childhood Cancer

Are You a Good Fit for This Trial?

This trial is for children and young adults up to 21 years old with high-risk neuroblastoma. Participants must have proper heart, liver, and kidney function, not have had more than one cycle of certain chemotherapies, and be able to undergo stem cell collection. Pregnant or breastfeeding individuals can't join; neither can those with conditions that might affect the study's results.

Inclusion Criteria

I have been diagnosed with neuroblastoma or ganglioneuroblastoma.

I was 21 years old or younger when first diagnosed.

All subjects and/or legal guardians must sign informed written consent

Exclusion Criteria

Subjects with any other medical condition deemed by the Investigator to interfere with the interpretation of the results or the subject's ability to cooperate and participate in the study

Lactating females are not eligible unless they have agreed not to breastfeed their infants

Subjects receiving any investigational drug concurrently

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive molecularly guided therapy in combination with standard chemotherapy

Cycles 3-6 (approximately 6 months)

Randomized Controlled Trial

Participants receive standard immunotherapy with or without DFMO

2 years

DFMO Maintenance

Participants receive DFMO BID for 730 days

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ceritinib
• Dasatinib
• DFMO
• Sorafenib
• Vorinostat

Trial Overview The study tests molecularly guided therapy combined with standard treatments for neuroblastoma. It includes a randomized trial comparing standard immunotherapy alone versus with DFMO (an investigational drug), followed by maintenance therapy using DFMO.

How Is the Trial Designed?

Group I: Standard Immunotherapy without DFMO Active Control 4 Interventions

One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days.

Group II: Standard Immunotherapy with DFMO Active Control 5 Interventions

One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days.

Ceritinib is already approved in United States for the following indications:

Approved in United States as Danyelza for:

• High-risk neuroblastoma in the bone or bone marrow

Who Is Running the Clinical Trial?

Giselle Sholler

Lead Sponsor

Trials

23

Recruited

2,500+

Giselle SaulnierSholler

Lead Sponsor

Trials

22

Recruited

2,400+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Beat NB Cancer Foundation

Collaborator

Trials

6

Recruited

1,300+

K C Pharmaceuticals Inc.

Industry Sponsor

Trials

5

Recruited

790+

Team Parker for Life

Collaborator

Trials

3

Recruited

1,100+

Dell, Inc.

Industry Sponsor

Trials

3

Recruited

740+

Published Research Related to This Trial

Activating mutations in the ALK gene are common in neuroblastoma, making it a key target for new treatments, as preclinical studies show that ALK inhibitors can effectively combat tumor growth.

The first approved ALK inhibitor, Crizotinib, has shown promising results in pediatric phase I trials for neuroblastoma, and a new international phase I study for the second-generation ALK inhibitor, LDK-378, is set to begin, expanding treatment options for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy for Neuroblastoma: ALK Inhibitors. Schulte, JH., Schulte, S., Heukamp, LC., et al.[2022]

FTY720 shows potent anti-cancer activity against neuroblastoma (NB) in preclinical models, effectively inducing cell death and inhibiting tumor growth, especially when combined with the chemotherapy drug topotecan.

The mechanism of action for FTY720 involves the inhibition of sphingosine kinase 2 and the alteration of sphingolipid levels, leading to a unique, caspase-independent cell death pathway that may enhance treatment strategies for advanced NB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway. Li, MH., Hla, T., Ferrer, F.[2021]

A high-content screening of 349 FDA-approved anticancer drugs identified ponatinib and axitinib as promising candidates for repurposing to treat high-risk neuroblastoma, showing effectiveness in inhibiting cell viability and inducing apoptosis in both 2D and 3D models.

Ponatinib demonstrated superior effects by consistently blocking cell migration and invasion, and it effectively inhibited tumor growth in mice with neuroblastoma, supporting its potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A High-Content Screening of Anticancer Compounds Suggests the Multiple Tyrosine Kinase Inhibitor Ponatinib for Repurposing in Neuroblastoma Therapy. Sidarovich, V., De Mariano, M., Aveic, S., et al.[2020]

Neuroblastoma, the most common childhood cancer, has a poor prognosis with a 5-year event-free survival rate of only 40% for high-risk patients, despite advancements in chemotherapy and maintenance therapies.

Novel targeted therapies, such as ALK inhibitors (like crizotinib and TAE684) and aurora kinase A inhibitors (like MLN8237), show promise in treating neuroblastoma by specifically targeting genetic mutations and may lead to more personalized treatment plans based on individual tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of treatment strategies for advanced neuroblastoma. Hara, J.[2021]

In a study of 34 patients with high-risk neuroblastoma who did not respond completely to initial therapy, the combination of naxitamab, irinotecan, temozolomide, and GM-CSF showed a complete response rate of 29% and a significant improvement in overall survival (OS) and event-free survival (EFS) when treatment was started early.

Patients receiving early treatment (cohort 1) had a 3-year OS of 84.8% and EFS of 54.4%, which were significantly better than those in the late treatment group (cohort 2), highlighting the importance of timing in administering this chemo-immunotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes. Muñoz, JP., Larrosa, C., Chamorro, S., et al.[2023]

The combination treatment of irinotecan, temozolomide, dintuximab, and GM-CSF (I/T/DIN/GM-CSF) showed significant antitumor activity in patients with relapsed or refractory neuroblastoma, with an overall objective response rate of 41.5% across 53 patients.

The treatment was associated with a one-year progression-free survival rate of 67.9% and an overall survival rate of 84.9%, although it also resulted in notable grade ≥ 3 toxicities, including fever/infection and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. Mody, R., Yu, AL., Naranjo, A., et al.[2021]

The FDA has approved dinutuximab, marking a significant advancement in the treatment of high-risk neuroblastoma, as it is the first major new therapy for this condition in over ten years.

Dinutuximab is used in combination with three other agents, enhancing its efficacy in treating this aggressive form of cancer in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dinutuximab approved for high-risk neuroblastoma. [2020]

A phase 1 study demonstrated that lorlatinib is both safe and effective for children with treatment-refractory or relapsed ALK-driven neuroblastoma, highlighting its potential as a new treatment option.

These preliminary findings suggest that lorlatinib could provide hope for young patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of lorlatinib against ALK-driven refractory or relapsed neuroblastoma. Suk, Y., Singh, SK.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40067131/

A phase II trial of Naxitamab plus stepped-up dosing of GM ... Results: Fifty-nine HR-NB patients (53 stage 4, 6 stage 3) were enrolled 2/2017-7/2020. At 36 months, EFS/OS were 73%/93%, but 50/59 patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6440722/

Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing ... In this phase 1 clinical trial of 57 patients with high-risk neuroblastoma, high doses of hu3F8 were well tolerated, without a need for inpatient monitoring.

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/761171Orig1s000MultidisciplineR.pdf

761171Orig1s000 - accessdata.fda.gov neuroblastoma based on results from clinical trials in patients aged 12 months and older. The FDA's Assessment: The effect of naxitamab on ...

4. nature.com nature.com/articles/s41467-025-56619-x

The anti-GD2 monoclonal antibody naxitamab plus GM ... Results from this prespecified interim analysis show statistically significant and clinically meaningful outcomes, with an ORR of 50% (95% CI: ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/31/10/1877/762209/A-Phase-II-Trial-of-Naxitamab-plus-Stepped-up

A Phase II Trial of Naxitamab plus Stepped-up Dosing of GM ... GM-CSF significantly improves outcome with murine-3F8. In an international trial, naxitamab + GM-CSF was effective against chemoresistant HR-NB, leading to ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)43076-5/fulltext

75P Efficacy and updated safety results from pivotal phase ... 75P Efficacy and updated safety results from pivotal phase II trial 201 of naxitamab (Hu3F8): A humanized GD2-targeted immunotherapy for the treatment of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06013618?term=Naxitamab&rank=10

NCT06013618 | Clinical Analysis of Naxitamab (hu3F8) in ... This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or combined with chemotherapy or combined with chemotherapy and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02650648

NCT02650648 | Humanized Anti-GD2 Antibody Hu3F8 and ... This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with hu3F8 in high-risk NB patients.