Tipifarnib + Naxitamab for Neuroblastoma

Recruiting at 2 trial locations

Overseen By BCC Enroll

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Giselle Sholler

Must not be taking: Investigational drugs, Anticancer agents

Disqualifiers: Age <1 year, Uncontrolled infection, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for individuals with relapsed or hard-to-treat neuroblastoma, a type of cancer. It combines an investigational drug, tipifarnib (a pill), with an approved drug, naxitamab (administered through an IV), to evaluate their safety and effectiveness together. The study aims to determine how well this combination prevents the disease from returning or worsening. Individuals diagnosed with neuroblastoma, whose disease has returned or not fully responded to previous treatments, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants stop taking other anti-cancer medications before joining. There are specific waiting periods after previous treatments, like 2 weeks for chemotherapy and 4 weeks for immunotherapy, before starting the trial.

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

Previous studies have examined the safety of using tipifarnib with naxitamab in patients, aiming to assess how well patients tolerate this combination. Tipifarnib is an investigational drug, while naxitamab has FDA approval for certain types of neuroblastoma, a kind of cancer.

The studies suggest that the combination is generally well-tolerated. Patients did not report any unexpected side effects, though individual reactions may vary. Common side effects from naxitamab alone might include pain or allergic reactions during treatment, which could also occur with this combination.

Since the study is in Phase 2, researchers have already gathered some safety information from earlier phases. This provides some evidence that the treatment could be safe, but more data is needed for confirmation. Consulting a healthcare provider is crucial to determine if this study aligns with personal health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tipifarnib and Naxitamab for treating neuroblastoma because they offer a fresh approach to tackling this challenging cancer. Unlike standard treatments like chemotherapy, which attack rapidly dividing cells broadly, Tipifarnib specifically targets enzymes involved in cancer cell growth, offering a more focused attack on the cancer itself. Naxitamab, on the other hand, is an antibody that binds to a protein on neuroblastoma cells, helping the immune system recognize and destroy them more efficiently. This combination could potentially lead to more effective and less toxic treatment options for patients.

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

This trial will evaluate the combination of Tipifarnib and Naxitamab for treating neuroblastoma. Studies have shown that using Tipifarnib with Naxitamab could be promising for this purpose. Naxitamab is already approved for certain types of neuroblastoma and has helped some patients fully recover. Research suggests that Tipifarnib enhances treatments like Naxitamab by boosting the immune system's ability to fight cancer cells. Patients who previously received Naxitamab-based treatments experienced better long-term results. This combination might offer new hope for those with challenging cases of neuroblastoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Giselle SaulnierSholler, MD

Principal Investigator

Beat Childhood Cancer

Are You a Good Fit for This Trial?

This trial is for patients with neuroblastoma that has come back or hasn't responded to treatment. Participants must have had some response or stable disease after previous therapy and be suitable for taking tipifarnib orally and receiving naxitamab intravenously.

Inclusion Criteria

I have given my written consent to participate.

My organs are functioning well enough for me to join the trial.

My diagnosis of neuroblastoma has been confirmed by a pathology report.

Exclusion Criteria

BSA of <0.25 m2

Subjects who are currently receiving another investigational drug

Subjects who are currently receiving other anticancer agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tipifarnib and Naxitamab. Tipifarnib is administered on days 1-7 and 15-21 of each 28-day cycle, and Naxitamab is administered intravenously on Days 1, 3, and 5 of each cycle.

6 months

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety, tolerability, and progression-free survival after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Naxitamab
• Tipifarnib

Trial Overview The study tests the safety and effectiveness of combining tipifarnib, a pill, with naxitamab, an IV drug approved by the FDA for certain cases of neuroblastoma. The goal is to see how well patients respond to this combination and how long they live without their cancer worsening.

How Is the Trial Designed?

Group I: HRNB Bone/Bone Marrow Experimental Treatment 2 Interventions

Cycles 1-6: Tipifarnib and Naxitamab Tipifarnib: on days 1-7 and 15-21 of each 28-day cycle. Naxitamab IV on Days 1, 3, and 5 of each cycle.

Group II: HRNB All others Experimental Treatment 2 Interventions

Cycles 1-6: Tipifarnib and Naxitamab Tipifarnib: on days 1-7 and 15-21 of each 28-day cycle. Naxitamab IV on Days 1, 3, and 5 of each cycle.

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

Approved in United States as Danyelza for:

• High-risk neuroblastoma in bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy

Who Is Running the Clinical Trial?

Giselle Sholler

Lead Sponsor

Trials

23

Recruited

2,500+

Published Research Related to This Trial

Naxitamab is a humanized monoclonal antibody specifically designed to target GD2-positive cancers, including neuroblastoma and osteosarcoma, and has received accelerated approval from the US FDA for treating high-risk neuroblastoma in pediatric and adult patients.

The approval allows naxitamab to be used in combination with granulocyte-macrophage colony-stimulating factor for patients who have shown a partial or minor response, or stable disease after previous treatments, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naxitamab: First Approval. Markham, A.[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]

Naxitamab, a humanized monoclonal antibody targeting GD2, was approved by the FDA in 2020 for treating relapsed/refractory high-risk neuroblastoma in pediatric and adult patients, showing promise in combination with GM-CSF.

Clinical experience from Sant Joan de Déu Children's Hospital indicates that naxitamab can be effectively administered alone or with chemotherapy agents like irinotecan and temozolomide, with strategies in place for managing adverse events, including pain during infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How we approach the treatment of patients with high-risk neuroblastoma with naxitamab: experience from the Hospital Sant Joan de Déu in Barcelona, Spain. Castañeda, A., Gorostegui, M., Miralles, SL., et al.[2022]

In a study of 33 infants with high-risk neuroblastoma, anti-GD2 monoclonal antibodies (3F8 and naxitamab) were administered safely during or immediately after chemotherapy, with manageable side effects and no severe long-term toxicities reported.

The treatment showed promising long-term outcomes, with 17 out of 21 patients receiving 3F8 in complete remission after a median of 13.4 years, and 10 out of 12 naxitamab patients remaining relapse-free after a median of 3.1 years, indicating that high-risk neuroblastoma in infants can be highly curable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. Kushner, BH., Modak, S., Kramer, K., et al.[2022]

In a study of 73 high-risk neuroblastoma patients in complete remission, treatment with naxitamab and GM-CSF resulted in a three-year overall survival rate of 82.4% and an event-free survival rate of 58.4%.

The treatment was generally well-tolerated, with only 5% of patients experiencing severe grade 4 toxicities, and the majority (79.5%) completed the therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. Mora, J., Castañeda, A., Gorostegui, M., et al.[2022]

In a Phase II pilot study involving 23 children with untreated high-risk neuroblastoma, the combination of gefitinib and irinotecan showed mild and reversible toxicity, with common side effects including nausea and diarrhea.

While the treatment resulted in some partial responses and tumor volume reductions, the overall response rate was not high enough to justify further investigation, indicating that this combination may not be effective enough for broader clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-arm pilot phase II study of gefitinib and irinotecan in children with newly diagnosed high-risk neuroblastoma. Furman, WL., McGregor, LM., McCarville, MB., et al.[2021]

Naxitamab, a monoclonal antibody for treating high-risk neuroblastoma, has a safety profile where over 50% of pediatric patients experienced manageable adverse events like pain, hypotension, and bronchospasm, with some severe cases requiring careful monitoring.

The study emphasizes the importance of premedication and supportive therapies to manage these adverse events effectively, allowing patients to continue treatment and maximize the benefits of naxitamab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events. Mora, J., Chan, GC., Morgenstern, DA., et al.[2023]

Citations

1. archildrens.org archildrens.org/research/clinical-trials/tipifarnib-and-naxitamab-for-neuroblastoma-study

Phase II Trial of Tipifarnib and Naxitamab for Relapsed/ ... While cure rates have improved with current treatment approaches, outcomes are poor for patients who have refractory disease after intensive upfront treatment ...

2. trial.medpath.com trial.medpath.com/news/f1643d8f5cea76e8/penn-state-college-of-medicine-beat-childhood-cancer-research-consortium-leading

New Clinical Trial Tests Tipifarnib and Naxitamab ... - MedPath Preclinical studies have demonstrated that tipifarnib enhances the efficacy of anti-GD2 monoclonal antibodies like naxitamab against neuroblastoma. The trial ...

3. trialx.com trialx.com/clinical-trials/listings/320924/tipifarnib-and-naxitamab-for-relapsedrefractory-neuroblastoma/

Tipifarnib and Naxitamab for Relapsed/Refractory ... Overview. The purpose of this study is to evaluate the investigational drug, tipifarnib (a pill taken by mouth), in combination with the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11276848/

Neuroblastoma—A Review of Combination Immunotherapy Tipifarnib was shown to significantly enhance dinutuximab-mediated tumor growth inhibition and prevent the immunosuppressive effects of NB-derived sEVs in vivo.

5. withpower.com withpower.com/trial/phase-2-recurrent-neuroblastoma-9-2024-c69d6

Tipifarnib + Naxitamab for Neuroblastoma In one study, patients receiving Naxitamab-based therapy had improved long-term outcomes, with a significant number achieving complete remission.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01394

Tipifarnib and Naxitamab for Relapsed/Refractory ... The purpose of this study is to evaluate the investigational drug, tipifarnib (a pill taken by mouth), in combination with the Food and Drug Administration ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03363373

NCT03363373 | Naxitamab for High-Risk Neuroblastoma ... A pivotal phase 2 trial of antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in high-risk neuroblastoma patients.