Tipifarnib + Naxitamab for Neuroblastoma

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Giselle Sholler

Must not be taking: Investigational drugs, Anticancer agents

Disqualifiers: Age <1 year, Uncontrolled infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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 (FDA) approved drug, naxitimab, administered intravenously (IV; a liquid that continuously goes into your body through a tube that has been placed during a surgery into one of your veins). Naxitamab is FDA approved for pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy, it may not be approved in the type of disease used in this study. The goals of this part of the study are: * Test the safety and tolerability of tipifarnib in combination with naxitimab in patients with cancer * To determine the activity of study treatments chosen based on: * How each subject responds to the study treatment * How long a subject lives without their disease returning/progressing

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.

What data supports the effectiveness of the drug combination Tipifarnib and Naxitamab for treating neuroblastoma?

Research shows that Naxitamab, when combined with other treatments, has been effective in treating high-risk neuroblastoma, especially when used early in the treatment process. In one study, patients receiving Naxitamab-based therapy had improved long-term outcomes, with a significant number achieving complete remission. ^{1 2 3 4 5}

Is the combination of Tipifarnib and Naxitamab safe for treating neuroblastoma?

Naxitamab, used in combination with other treatments for neuroblastoma, has been associated with some side effects like pain, high blood pressure, and diarrhea, but these were generally manageable. Serious side effects occurred in a significant number of patients, but the treatment was still considered safe enough for outpatient administration. ^{1 2 3 4 6}

What makes the drug Tipifarnib + Naxitamab unique for treating neuroblastoma?

The combination of Tipifarnib and Naxitamab is unique because Naxitamab is a humanized monoclonal antibody that specifically targets GD2, a molecule found on neuroblastoma cells, and has been approved for use in patients with relapsed or refractory high-risk neuroblastoma. This drug is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance its effectiveness, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 4 7}

Research Team

Giselle SaulnierSholler, MD

Principal Investigator

Beat Childhood Cancer

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Naxitamab (Monoclonal Antibodies)
• Tipifarnib (Other)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Giselle Sholler

Lead Sponsor

Trials

23

Recruited

2,500+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2023]

2. Switzerland 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. [2023]

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

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Naxitamab: First Approval. [2021]

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

A single-arm pilot phase II study of gefitinib and irinotecan in children with newly diagnosed high-risk neuroblastoma. [2021]

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

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. [2022]

7. England 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. [2022]